Bipolar disorder is a leading cause of disability that is characterized by cycling among emotional extremes. The underlying neurophysiology of bipolar disorder may involve dysfunction of frontal-subcortical networks that maintain emotional homeostasis, termed the 'anterior limbic network.'Anterior limbic network (ALN) dysfunction may underlie the dysfunctional impulsivity that is a characteristic symptom of bipolar disorder, as well as other psychiatric disorders. Dysfunctional impulsivity is a multi-dimensional construct consisting of at least three behavioral components: inability to delay gratification, distractibility, and disinhibition. Inability to delay gratification results fom enhanced sensitivity to immediate reward, and may underlie the poor decision-making and comorbid substance abuse commonly seen in bipolar disorder patients. Generally, delayed rewards are valued less than immediate rewards, a process called delay discounting. Impulsive individuals including psychiatric patients, show greater delay discounting than healthy control subjects. This project investigates the neural mechanism of impulsivity and reward processing in bipolar disorder using a delay discounting task where subjects decide between monetary gains at different times. We will investigate whether frontal-subcortical dysfunction underlies greater rates of delay discounting in manic bipolar patients by collecting both behavioral and fMRI data in order to demonstrate alterations in delay discounting between bipolar patients and healthy subjects.
The innovative aspects of this proposal are the utilization of both laboratory and psychometric tests of impulsivity during mania, and the correlation of these laboratory findings with neural activity as measured by fMRI. Establishing the neural mechanisms that underlie impulsivity and reward processing in bipolar disorder will provide insight into how dysfunctional reward processing provides a foundation for the counterproductive and clinically relevant impulsivity seen in bipolar disorder. This research will contribute to future efforts to identify treatments for bipolar disorder by providing a clearer model of the deficient neurophysiology responsible for bipolar patients'inability to delay gratification and the resulting dysfunctional impulsivity.
|Strakowski, Stephen M; Eliassen, James C; Lamy, Martine et al. (2011) Functional magnetic resonance imaging brain activation in bipolar mania: evidence for disruption of the ventrolateral prefrontal-amygdala emotional pathway. Biol Psychiatry 69:381-8|