Tuesday, April 23, 2024
4/23/2024
PROJECT SUMMARY Anhedonia, defined as a reduced interest in or motivation for rewards, is a core symptom of depression that has been linked to reduced treatment response and increased risk of suicide. A key risk factor for the development of anhedonia is chronic stress, which has further been shown to impact function within the mesolimbic dopamine (DA). DA is a key neurotransmitter for motivation; both clinical and preclinical studies have shown that dopamine depletion reduces willingness to expend effort. To date, however, human studies linking dysregulation of dopamine to stress-induced anhedonia are lacking. This is due in part to the challenges associated with taking in vivo measurements of dopamine in humans. Dopamine activity is commonly measured in human studies using positron emission tomography (PET) imaging. PET is a popular neuroimaging technique used to provide measurements of dopamine activity. However, it is costly, invasive, and necessitates exposure to radiation. These factors make it difficult to conduct large scale studies. Neuromelanin magnetic resonance imaging (NM-MRI) is a relatively new non-invasive imaging technique used to take proxy measurements of dopamine. NM-MRI works by imaging neuromelanin, a pigment that accumulates in high concentrations in dopamine neurons, over the lifespan. Prior studies have shown that NM- MRI signal is correlated with PET signal. In short, NM-MRI can provide proxy measurements of dopamine without the same limitations posed by PET. In the current study, we will examine associations between NM- MRI signal and behavioral and neural measures of motivational anhedonia. We will also explore the relationship between NM-MRI signal and fMRI measures of corticostriatal circuit function. Lastly, we will examine the relationship between NM-MRI signal and physiological and self-report measures of stress. By completing this study, the PI will gain the opportunity to grow as an independent researcher and become a more competitive post-doctoral candidate.
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