Grant: CIHR Fellowship

From deciding whether to snack on a cupcake or a carrot, to whether we should spend frivolously or save for retirement, we are continuously confronted with choices between immediate reward and delayed gratification. Numerous social, physical, and mental health benefits accrue to people who can forgo immediate gratification in the service of long-term goals and plans. By contrast, impulsive decision making is evident across a wide variety of mental illnesses, including schizophrenia and substance abuse. While prior research has identified some of the neurobiological substrates for this cost/benefit decision making, the mechanisms underlying its disruption in illness remain elusive. Here, we propose to leverage the strengths of two complementary brain-imaging methods to test a novel circuit-based hypothesis for impulsive decision making. According to this hypothesis, impulsive choice behaviour results from deficient regulation of the striatum (a brain region that responds to rewards and reward cues) by lateral prefrontal cortex (a region that maintains information about the consequences of one's actions, and also represents long-term goals). Work in rodents suggests that the ability of prefrontal cortex to regulate striatal function is dependent on the neurotransmitter glutamate. We will use functional magnetic resonance imaging (fMRI) to measure striatal response during a reward decision-making task, and magnetic resonance spectroscopy to measure prefrontal glutamate levels. We predict that 1) prefrontal glutamate and striatal reward response will be inversely correlated, 2) more impulsive subjects will have lower prefrontal glutamate, and 3) that the relationship between prefrontal glutamate and impulsivity will be mediated by striatal reward response. This proposal will reveal a novel biological mechanism for impulsive choice behaviour, paving the way for more effective therapeutic interventions in an area where few currently exist.