The use of methamphetamine (MA) despite negative consequences such as health, legal and social problems reflects maladaptive behaviors, such as acting without forethought and failure to delay gratification or to withhold inappropriate responses. Such behaviors can broadly be characterized as reflecting impulsivity, which is thought to contribute to addictions. The overarching goal of the proposed work is to help clarify the neural networks that underlie impulsive behavior and to determine how the structural integrity of these networks influences impulsive behaviors in healthy and MA-dependent individuals. A temporal discounting task, which is thought to reflect impulsive choice, will be used to measure how the subjective value of a reinforcer diminishes as a function of time. It requires that participants choose between smaller, more immediate rewards and larger, delayed rewards. As task performance likely depends on neural circuitry important for assessing subjective value of rewards, comparison of two options presented, and ultimately selecting one option over the other, structural magnetic resonance imaging will be used to measure the gray matter integrity of frontal, parietal, and limbic cortices, which may contribute to these cognitive processes. Diffusion tensor imaging will be used to determine white matter integrity of the pathways connecting these structures. The immediate goals of this work are to determine the relationship between temporal discounting and brain structure in healthy individuals, to assess whether MA-dependent participants have structural abnormalities in the implicated circuitry, and to determine whether the normal relationship between brain structure and temporal discounting holds under conditions of potential MA-induced neuropathology. Lastly, a self-report measure of trait impulsivity will be used to determine if the integrity of the neural networks implicated in temporal discounting also contribute to individual differences in a broader assessment of the construct of impulsivity. As there are currently no pharmacological treatments approved for MA-dependence, impulsive behaviors are especially problematic because they undermine the success of behavioral treatments for drug dependence. This information could inform treatments for addictive disorders resulting in improved treatment retention and lower rates of relapse.

Public Health Relevance

Amphetamine-type stimulants (including methamphetamine) are the second most commonly used illicit drug worldwide making methamphetamine abuse and dependence a substantial problem for affected individuals, their families and the general public. Impulsive behaviors exhibited by methamphetamine-dependent individuals may undermine the success of behavioral therapies, the only treatment option available for methamphetamine dependence. Knowledge of the neural substrates of impulsivity and of the integrity of these substrates in MA-dependent individuals has the potential to inform treatment options.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F02A-J (20))
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Bjork, James M
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University of California Los Angeles
Schools of Medicine
Los Angeles
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London, Edythe D; Kohno, Milky; Morales, Angelica M et al. (2015) Chronic methamphetamine abuse and corticostriatal deficits revealed by neuroimaging. Brain Res 1628:174-85
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Kohno, Milky; Morales, Angelica M; Ghahremani, Dara G et al. (2014) Risky decision making, prefrontal cortex, and mesocorticolimbic functional connectivity in methamphetamine dependence. JAMA Psychiatry 71:812-20
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