Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) have aberrant feeding behavior and disturbances of emotionality and impulse control, which are thought to be related to dysfunction of limbic and cognitive circuits. The parent application will use blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine neural substrates underlying appetitive (AIM 1), reward (AIM 2), and cognitive (AIM 3) dysregulation in AN and BN participants and correlate BOLD signals with behavior (AIM 4). Over 5 years, we will study 50 women recovered (REC) from AN and 50 female REC BN, comparing them to 50 healthy control women (CW), all of whom are 18 to 45 years old. (We are studying women recovered from these disorders to avoid the confounding effects of malnutrition and because considerable data suggest that these symptoms are traits that persist after recovery). In order to accelerate understanding of structure and perfusion of limbic and cognitive neural pathways in AN and BN, this revised application adds the following advanced imaging tools: 1) Morphometry with proton density (PD) and T2-weighted images to aid in grey and white matter volumetric evaluation;2) Diffusion Tensor Imaging (DTI) to assess white matter and for mapping fiber tracts;and 3) Arterial Spin Labeling (ASL) to collect perfusion measures. This revision will employ these structural and perfusion tools in AIM 5 to investigate 24 REC AN, 24 REC BN, and 24 CW from the parent grant over a 2 year period. Limbic and cognitive regional disturbances may be traits that represent the neuropathic manifestation of a genetic vulnerability in those with AN and BN.
In AIM 5 A, we expect structural and perfusion imaging will support the hypothesis that AN and BN have similar alterations within limbic brain regions, which contribute to emotional dysregulation, but have different vulnerabilities for inhibitory self-control involving dorsal cognitive circuit disturbances. Alternatively, structure and perfusion studies may shed light on more complex patterns of imbalances of neural processes.
In AIM 5 B, we will determine whether REC AN and BN have diffuse, global """"""""scars"""""""" secondary to years of malnutrition. For example, diffuse """"""""scars"""""""" may affect white matter density and organization, since brain white matter growth peaks during adolescence and thus may be permanently compromised by starvation.
AIM 5 C will explore relationships between structure and perfusion imaging and behavior, cognition, and fMRI measures. Considered together, these imaging studies will enable us to better characterize cognitive and limbic dysfunction in these populations and will shed light on whether abnormal brain processes after recovery are """"""""scars"""""""" or traits. Understanding biologic vulnerabilities in AN and BN is critical for developing effective treatment interventions for these often chronic and deadly disorders.
The parent application will employ functional magnetic brain imaging to probe brain circuits modulating appetite, reward, and impulse control in anorexia and bulimia nervosa. The revision accelerates progress of the neurobiology of eating disorders by adding brain structure and perfusion imaging studies;and longitudinal and brain development milestone studies of anorexia nervosa.
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