Various neuropsychiatric disorders, especially addictions, feature impairments in risky decision-making; clarifying the neural mechanisms underlying this problem can inform treatment.
To determine how methamphetamine-dependent and control subjects differ in brain activation during a risky decision-making task, resting-state functional connectivity within mesolimbic and executive control circuits, and the relationships between these measures.
A case-control, functional magnetic resonance imaging study of methamphetamine-dependent and healthy comparison participants at rest and when performing the Balloon Analogue Risk Task, which involves the choice to pump a balloon or to cash out in the context of uncertain risk.
Clinical research center at an academic institution.
Twenty-five methamphetamine-dependent and 27 control subjects.
Main Outcomes and Measures
1) Parametric modulation of activation in the striatum and right dorsolateral prefrontal cortex, i.e., the degree to which activation changed as a linear function of risk and potential reward, both indexed by pump number; and 2) resting-state functional connectivity, measured in whole brain with seeds in the midbrain and right dorsolateral prefrontal cortex. Relationships between these outcomes were also tested.
Parametric modulation of cortical and striatal activation by pump number during risk-taking differed with group. It was stronger in the ventral striatum but weaker in the right dorsolateral prefrontal cortex in methamphetamine-dependent participants than controls. Methamphetamine-dependent subjects also exhibited greater resting-state functional connectivity of the midbrain with the putamen, amygdala, and hippocampus. This connectivity was negatively related to modulation of right dorsolateral prefrontal cortex activation by risk level during risky decision-making. In controls, parametric modulation of right dorsolateral prefrontal cortex activation by risk during decision-making was positively related to resting-state functional connectivity of the right dorsolateral prefrontal cortex with the striatum.
Conclusions and Relevance
Maladaptive decision-making by methamphetamine users may reflect circuit-level dysfunction, underlying deficits in task-based activation. Heightened resting-state connectivity within the mesocorticolimbic system, coupled with reduced prefrontal cortical connectivity, may create a bias toward reward-driven behavior over cognitive control in methamphetamine users. Interventions to improve this balance may enhance treatments for stimulant dependence and other disorders that involve maladaptive decision-making.