2007 — 2011 |
Feusner, Jamie |
K23Activity Code Description: To provide support for the career development of investigators who have made a commitment of focus their research endeavors on patient-oriented research. This mechanism provides support for a 3 year minimum up to 5 year period of supervised study and research for clinically trained professionals who have the potential to develop into productive, clinical investigators. |
Body Dysmorphic Disorder: Clinical and Neurobiological Features @ University of California Los Angeles
DESCRIPTION (provided by applicant): This proposal describes the five-year K23 Mentored Patient-Oriented Research Career Development Award of Jamie Feusner, M.D. The overall goals are to provide him with the conceptual background and research skills necessary to conduct patient-oriented research on body dysmorphic disorder (BDD). The candidate will train in functional neuroanatomy, functional neuroimaging, neuropsychological testing, biostatistics, research design, standardized assessment, and research ethics. He will received guidance from his mentors Drs. Susan Bookheimer and Alexander Bystritsky as well as outside consultants in an organized program of supervised research and coursework at UCLA and the BDD Research Unit at Massachusetts General Hospital, and the BDD research lab at Brown University. BDD occurs in approximately 1-2% of the population. It is a severe and disabling psychiatric condition with a lifetime suicide attempt rate of 25%, yet is vastly underrecognized and understudied. Individuals with BDD are obsessed with perceived defects in their appearance and experience extreme shame, anxiety and dysphoria related to them. When viewing themselves and others, they tend to focus on specific details of skin, hair, noses, etc. This, and neuropsychological data, suggest that impaired visual information processing may underscore the pathophysiology. The goal of the proposed project is to study visual processing in individuals with BDD using functional magnetic resonance imaging (fMRI). In the first phase of the study regional brain activation patterns will be compared in individuals with BDD vs. controls, with respect to the processing of high and low-spatial frequency (level of detail) when viewing others'faces. The results will indicate if BDD subjects process faces preferentially using regions/networks of the brain responsible for high- detail processing. In the second phase, fMRI will similarly be used to identify regional brain activation patterns for a task involving processing of photographs of the subjects'own faces (that they perceive are defective) in order to determine further visual processing abnormalities activated with emotional arousal. Relevance: Determining patterns of visual processing in body dysmorphic disorder potentially could be used to develop focused, long-term effective treatments that address correcting the core abnormal processes that contribute to the symptoms. This project will also allow Dr. Feusner to meet his training objectives.
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0.915 |
2011 — 2014 |
Feusner, Jamie O'neill, Joseph [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Cognitive-Behavioral Therapy and Glutamate in Cingulate Gyrus in Ocd @ University of California Los Angeles
DESCRIPTION (provided by applicant): This study will characterize the neurochemical abnormalities in important brain circuits underlying obsessive-compulsive disorder (OCD) symptoms and the effects of cognitive-behavioral therapy (CBT). Identification of such metabolite biomarkers will provide an important foundation for translational clinical studies to maximize the ability of CBT to reduce symptoms and to design medications that target core features of the disease, which is particularly important for those who do not respond to, or have access to, CBT. This is relevant to the NIMH strategic plans to promote discovery in the brain of the causes of mental disorders and will help lay the foundation for the development of new and better interventions that incorporate the diverse needs and circumstances of people with mental illnesses. OCD is an often disabling and chronic psychiatric condition that affects approximately 2% of the world's population. Most patients respond only incompletely to current treatments and many do not respond at all. CBT, a form of psychotherapy, is one of the most effective treatments for OCD, yet its mechanism of action is not fully understood. The objective of this proposed study is to use neuroimaging to understand how neurometabolite abnormalities in neural circuits relate to OCD symptoms, and how these are affected by CBT. In OCD, dysfunction is suspected in several subregions of the cingulate gyrus, a brain region involved in relevant neural circuits. This proposal will use magnetic resonance spectroscopic imaging (MRSI) to measure concentrations of brain metabolites, including glutamate (Glu), in the cingulate. Glu is an important excitatory neurotransmitter that is suspected to be disturbed in OCD. In this proposal, MRSI scans will be performed on 25 adult OCD patients before and after 4 weeks of daily CBT. They will be compared to 25 untreated healthy controls scanned 4 weeks apart. A third group of 25 OCD patients will be scanned before and after 4 weeks while on the waitlist, will then receive 4 weeks of CBT, and will be scanned a third time at its completion. The specific aims of this proposal are: 1) Determine if levels of the Glu in the emotional and cognitive subregions of the cingulate differ between OCD patients and controls; 2) Determine if Glu changes after CBT or waitlist in the OCD patients and if they change in the controls after simple passage of time; 3) Determine if there are relationships between Glu and clinical and neurocognitive symptoms of OCD before and after CBT.
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0.915 |
2011 — 2015 |
Feusner, Jamie |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Common and Distinct Phenotypes of Body Dysmorphic Disorder and Anorexia Nervosa @ University of California Los Angeles
DESCRIPTION (provided by applicant): The purpose of this study is to characterize shared and unique brain circuits associated with Body Dysmorphic Disorder (BDD) and Anorexia Nervosa (AN) using a set of functional neuroimaging experiments. BDD and anorexia nervosa AN are severe and disabling psychiatric disorders that share many clinical features such as distorted body image and overvaluation of appearance for self-worth, yet they are currently classified in separate diagnostic categories. Despite their significant morbidity and mortality, very little research has been conducted to compare and contrast these disorders in order to understand the underlying neurobiology of shared and unique clinical phenotypes. An important shared clinical phenotype in BDD and AN is perceptual distortion of appearance, which may contribute to distorted body image. There is early evidence of similar, common phenotypes of disturbances in visual perception and visuospatial processing in BDD and AN, as evidenced clinically and from neuropsychological testing. However, little is known of the underlying neurobiological processes that mediate these. A preliminary functional magnetic resonance imaging (fMRI) study in adults with BDD demonstrated abnormal activation in left hemisphere regions responsible for high-detail processing when viewing others' faces. A more recent study in BDD demonstrated no abnormalities of primary emotional processing regions when viewing own-faces. AN, on the other hand, is often characterized by early, childhood-onset anxiety in addition to extreme fears of weight gain. However, no study has specifically examined fear processing in AN nor compared it to BDD. The goal of the proposed study is to define the common and distinct and phenotypes of visual and emotional processing in BDD and AN that map onto specific brain systems. This study will enroll 25 subjects with BDD, 25 with weight-restored AN, and 25 healthy controls, ages 18-30. Functional magnetic resonance imaging (fMRI) will be used to identify key abnormalities in brain systems associated with visual and emotional processing. Based on previous fMRI research in BDD, and our pilot data and previous studies suggesting abnormalities of detail-processing in AN, this study will investigate visual processing of others' faces, bodies, and non-face objects (houses) using different types of visual images that convey high, low, or normal level of detail. To compare and contrast patterns of emotional processing, this study will use fearful face stimuli to understand common or distinct brain activity patterns associated with emotional reactivity, regulation, and habituation. .
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0.915 |
2015 — 2019 |
Feusner, Jamie |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Anxiety and Reward Interaction and Prediction of Outcomes in Anorexia Nervosa @ University of California Los Angeles
? DESCRIPTION (provided by applicant): The purpose of this study is to understand the effects of anxiety on reward responsiveness in adolescents with anorexia nervosa (AN), and how this interaction predicts clinical outcome subsequent to intensive treatment. AN is notorious for its resistance to interventions and for the highest mortality rate of all psychiatric disorders. Variou forms of intensive treatment may succeed in restoring weight, yet overall benefits of treatment remain limited and early relapse is unusually high. While evidence suggests that genetic factors play a role in susceptibility, remarkably little is known about AN's mechanistic neural circuitry. Individuals with AN typically exhibit prodromal anxiety early in life prior to disordered eating. This phenotypic expression may manifest as exaggerated threat perception, and hypersensitivity to and avoidance of signals of weight and shape change. In parallel, individuals with restricting-type AN, beginning in early childhood, are reticent to exposure to novel and high reward environments. This is in line with most psychometric and neuroimaging studies that suggest low responsiveness to natural rewards, as well as aberrant reward system activity and dopaminergic function. However, the interaction between anxiety and reward circuits has never been interrogated in AN. There is substantial evidence of distinct yet overlapping neural systems mediating approach (related to reward) and avoidance (related to anxiety), which are integrated in balancing and switching between behaviors related to the predominant valence state. Thus, we posit that high degrees of reactivity of cortico-limbic circuits underlying anxiety may contribute to diminished capacity to respond to reward stimuli. This may translate clinically to lower motivation to engage in treatment; in effect, a lower drive to change behaviors and thought patterns necessary for improvement based on expectancy of benefits of future outcome, resulting in a course trajectory of weight loss and worsening of symptoms. Accordingly, this study investigates this anxiety and reward interaction in individuals with AN who have recently completed intensive treatment, and whom will be followed for degree of symptom relapse over 6 months. Forty two adolescents with restricting-type AN and 42 matched controls will engage in reward tasks in which individually- tailored anxiety provoking word stimuli are interleaved, while undergoing functional magnetic resonance imaging (fMRI). Reward and anxiety neural circuit activity, and their interaction, will be analyzed in relationship to their ability to predict trajetory of BMI and symptom severity changes over the subsequent 6 months. Using novel designs for interrogating the functionality of positive and negative valence circuits may thus lead to identification of dimensional phenotypes associated with disease persistence, a critical step towards developing individualized and targeted treatment strategies (such as reduction of stimuli-specific anxiety and/or enhancement of positive affect) for high-risk subgroups.
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0.915 |
2017 — 2020 |
Feusner, Jamie Savic-Berglund, Ivanka |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Gender Identity and Own Body Perception Implications For the Neurobiology of Gender Dysphoria @ University of California Los Angeles
Project Summary/Abstract Title: Gender identity and own body perception ? implications for the neurobiology of gender dysphoria Individuals with gender dysphoria (GD) experience a stark contrast between their gender identity and their gender assigned at birth. These individuals discover, early in development or later in life, that their body is incongruent with their gender identity. Persistent desire for the physical characteristics and social roles of the other sex contributes to dysphoria. Public awareness of the diversity of gender experience is rising, and issues of those with GD related to self-identity, body image, and medical interventions are becoming more openly discussed across the globe. As this is occurring, more and more individuals are considering, or actually undergoing, treatments to alter their hormones and physical body in attempt to better conform to their gender identity. These interventions, termed medical gender (identity) confirming interventions include gender confirming or sex reassignment surgery and cross sex hormone treatment. Many individuals will obtain these costly, usually irreversible, invasive, and sometimes risky measures to address incongruence between their gender identity and their body. This is quickly becoming a critical global health issue; yet there is very little understanding of what developmental, neurobiological, and sociocultural factors contribute to GD, and who may or may not benefit from these procedures, including those who experience gender ambiguity rather than dysphoria. However, studies of brain structure have found abnormalities in cerebral midline structures, and recent studies found differences in functional connectivity within resting state networks associated with self- referential thinking, as well as differences in the functional neural circuitry related to body perception. The purpose of this study is to address core symptoms of GD?dissatisfaction and estrangement from the own body, and self-referential thinking?by using behavioral experiments and functional and structural neuroimaging to investigate the cerebral networks mediating own body perception in individuals with GD compared to cis- sexual controls, and how they relate to subjective body self-incongruence. We will also investigate the longitudinal effects of estrogen and testosterone treatment on brain functional connections and body phenotype, and how brain structure/function, body phenotype, and hormones pre-treatment may predict who will benefit in terms of improvement of dysphoria and quality of life. As an exploratory aim we will investigate a novel body-morph visual processing task in its reliability and validity for research and clinical use. Studying individuals in both Sweden and the United States will additionally allow us to investigate the effect of stress related to differential cultural stigmatization of non-conforming gender roles. This study will provide valuable information on the neurobiological underpinning of GD and the effects of sex hormones, and promises to uncover functional or structural neural patterns that could predict outcome in terms of body image and quality of life after cross-sex hormone treatment, which ultimately could be used to assist in medical decision-making.
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0.915 |
2017 — 2018 |
Feusner, Jamie |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Understanding the Dynamics of Visual Processing Abnormalities in Body Dysmorphic Disorder @ University of California Los Angeles
Project Summary/Abstract Individuals suffering from body dysmorphic disorder (BDD) experience peculiar misperceptions of their appearance, most often of the face or head. With convictions of disfigurement and ugliness, they typically have poor insight or even delusional beliefs, as well as obsessive thoughts and compulsive behaviors, anxiety, and depression. These combine to result in significant difficulties in functioning, as well as depression, suicide attempts (25%), and psychiatric hospitalization (50%). Despite this severity, relatively few studies of the neurobiology, or even treatment studies, have been conducted in BDD. This underscores a critical need for research seeking to identify targets for intervention based on pathophysiological mechanisms. To-date, background research conducted by our group has provided early insights into neurobiological mechanisms that may contribute to these perceptual distortions, including prominent abnormalities in visual processing systems. These, along with evidence from neuropsychological and psychophysical tests of visuospatial and visual processing, have contributed to the development of a model of diminished global/holistic processing and enhanced detail processing, attributed to both ?top-down? and ?bottom-up? disturbances in perception. However, there remain gaps in the understanding of the neurobiology that may hinder the rational development of novel and effective treatment strategies. Studies thus far have primarily been cross-sectional and few have explored the effects of visual manipulation in order to probe for dynamic abnormalities. Accordingly, this study aims to illuminate the pathophysiology underlying perceptual distortions in BDD using two novel visual modulation techniques: a) attention modulation (?top-down?) and brief image presentation (?bottom-up?) to probe the visual system. We will enroll 34 individuals with BDD and 34 healthy controls, who will undergo two experiments involving viewing photographs of their face while being scanned using functional magnetic resonance imaging (fMRI). In the attention modulation experiment, they will be given instructions and training to hold their gaze constant in order to increase fixation duration and decrease scanning of appearance details, which we hypothesize will increase dorsal visual stream (global/holistic processing) and decrease ventral visual stream (local/detail processing) activation in the brain. In the second experiment we will test whether brief face viewing time increases activity in dorsal visual areas. Results from this study will advance our understanding of the neurobiological basis of perceptual distortions in BDD and identify neurobiological treatment targets for future testing of novel, translational perceptual retraining treatments.
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0.915 |
2020 |
Feusner, Jamie |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Mechanisms of Perceptual Abnormalities and Their Malleability in Body Dysmorphic Disorder. @ University of California Los Angeles
PROJECT SUMMARY Individuals with body dysmorphic disorder (BDD) misperceive specific aspects of their appearance to be conspicuously flawed or defective, despite these being unnoticeable or appearing miniscule to others. With convictions of disfigurement and ugliness, they typically have poor insight or delusional beliefs, obsessive thoughts and compulsive behaviors, anxiety, and depression. These result in significant difficulties in functioning, depression, suicide attempts (25%), and psychiatric hospitalization (50%). Despite this, relatively few studies of the neurobiology, and few treatment studies, have been conducted. This underscores a critical need for research to identify novel targets for intervention based on a comprehensive understanding of the pathophysiological mechanisms. Neuropsychological, behavioral, and neurobiological research by our group and others have uncovered mechanisms that may contribute to perceptual distortions, including prominent abnormalities in visual processing systems. These have contributed to a model of diminished global/holistic processing and enhanced local/detailed processing, attributed to ?bottom-up? and ?top-down? disturbances in perception. Using psychophysical experiments and novel visual modulation techniques, we have probed the brain?s visual systems responsible for global and local processing and found early evidence that they may be modifiable in BDD. These techniques include a ?top-down? attentional modulation and a ?bottom-up? perceptual modulation strategy. Abnormal eye gaze and emotional arousal when viewing faces may further contribute to abnormal perception. Whether these brain and behavior abnormalities are directly linked to abnormal perception remains to be understood. Accordingly, this study will determine a) if abnormalities in neural activation and connectivity in BDD when viewing one?s appearance are directly associated with abnormalities in perceptual functioning; and b) if changes in neural activation and connectivity from these visual modulation strategies are linked to changes in perceptual functioning, thus representing potential biomarkers. We will also determine how attentional systems, eye gaze behaviors and emotional arousal interact with brain functioning in visual systems, and with global and local perceptual functioning. We will enroll 80 participants with BDD, 40 with subclinical BDD, and 40 healthy controls who will undergo functional magnetic resonance imaging while viewing photographs of their, and others?, faces. We will obtain measures of global and local visual processing, emotional arousal while viewing their face, and eye gaze behaviors using eye tracking. To understand the malleability of global/local perception, and the neural mechanisms of these changes, we will determine whether repeated visual modulation using top-down and bottom-up strategies results in alterations of perceptual functioning and brain activity/connectivity, and relationships between them. Results will provide a comprehensive mechanistic model of abnormal visual information processing underlying the core symptom domain of misperceptions of appearance. This will lay the groundwork for next-step translational approaches.
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0.915 |
2021 |
Feusner, Jamie Savic-Berglund, Ivanka |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Personalized 3d Avatar Tool Development For Measurement of Body Perception Across Gender Identities @ University of California Los Angeles
Abstract Public awareness of the diversity of experiences of gender identities has climbed sharply. The specific issues of those with gender dysphoria (GD) related to self-identity, body image, and medical interventions are challenges for the 21st century, particularly given the high risk of suicide. Gender identity is tightly linked to one?s bodily features, particularly readily observable sexual characteristics. For transgender and nonbinary individuals with GD, the incongruence between their body associated with their birth-assigned sex ? what they see in the mirror before any treatment ? and the internalized representation of their gender-identified body is a key defining part of their experience and contributes to their dysphoria. Currently, no clinical or research tool exists to capture and quantify the diverse experiences of one?s current body and one?s gender-identified body (which may be distinct from their current body), across a range of gender identities. Measuring the internalized representation of one?s body could be facilitated by technology to visually represent this on a three-dimensional avatar. The technology needed to scan and analyze the human figure is now available and cost efficient. It is now possible to scan individuals to create personalized 3D visualizations, or ?avatars,? with which they can interact on mobile and desktop devices to represent internal representation of their bodies. This can allow individuals to see and manipulate their own 3D avatar with a high degree of flexibility. The goal of this project is to create a novel, visually based digital tool to measure, understand, and quantify individuals? experiences of their bodies. We will develop, validate, and test in transgender, nonbinary, and cisgender adults a personalized avatar tool to represent internalized gender-identified bodies in order to quantify incongruence between this and one?s current body. This tool ? ?GD Somatomap? ? will be an advancement over existing self-report questionnaires to capture visual representations of internalized body image, cross-sectionally and dynamically over time. It will be flexible enough to characterize the heterogenous experiences of a range of gender identities including binary transgender, gender fluid, nonbinary, and cisgender. It can be used in clinical and clinical research applications to track outcomes of cross-hormone and gender-affirming surgical treatments. It can potentially improve clinical outcomes by identifying specific sets of body parts as targets for treatments to improve body congruence. Further, it will provide a unique means to measure own-body perceptual accuracy; understanding differences in perceptual accuracy and what potentially modifiable factors contribute to this may have prognostic significance for treatments to address body incongruence. It could also be used in future studies to investigate functional and structural neurobiological correlates of body perception and internal body representation, and at what point in neurodevelopment these emerge for those with different gender identities.
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0.915 |