Download Neurophysiological Profiles of Reward

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Neurophysiological Profiles of Reward-Sensitivity in Bipolar Spectrum Symptoms
Bipolar disorder is the seventh leading cause of disability worldwide and affects one to
two percent of the United States population, according to the World Health Organization
(WHO). Past psychological research has linked mood disorders to individual differences in
reward-sensitivity, indicating that bipolar disorder is associated with high sensitivity to reward
(Nusslock et. al), whereas unipolar depression (without mania) is associated with low sensitivity
to reward (Pizzagalli, Jahn, OÕShea, 2005). However, the neurophysiology of reward-sensitivity
has been studied more extensively for depressive than bipolar symptoms. For my summer
project, I would like to investigate the relationship between individual differences in bipolar
symptoms and the neurophysiological profiles of reward-sensitivity. Examining this relationship
has the potential to elucidate the pathophysiology of bipolar disorder, identify biological markers
that differentiate between this disorder and unipolar depression, and develop treatments. With the
Undergraduate Research Grant (URG), I would be able to begin research this summer that I will
develop into a high-impact, and ideally, publishable study in the upcoming year for my senior
honors thesis.
Bipolar disorder is a severe, chronic illness associated with lower life expectancy and
high rates of unemployment, divorce, and suicide (Kasper and Hirschfeld, 2005). It involves both
depressive and manic episodes. Depressive episodes include feelings of persistent sadness, low
self-esteem, and/or loss of interest in previously enjoyable activities. In comparison, manic
episodes include abnormally elevated moods, which may involve periods of irritability or even
violence. Unipolar depression (without a history of mania) is characterized exclusively by
depressive episodes (Butcher, Mineka, Hooley, 2010). Individual differences in rewardsensitivity have been linked to both unipolar depression and bipolar disorder; unipolar depression
is associated with low sensitivity to reward cues, which is reflected in decreased goal-directed
behavior and depressed states (Pizzagalli et. al, 2005). In contrast, bipolar disorder is
characterized by hypersensitivity to rewarding stimuli, and excessive motivation is reflected in
manic symptoms (Nusslock et. al, 2007).
Recently, researchers have begun investigating the neurobiological foundation of
abnormalities in reward sensitivity in mood disorders. Studies using functional magnetic
resonance imaging (fMRI), a neuroimaging technique that measures changes in blood flow to
reflect brain activity, have demonstrated that depression is associated with blunted rewardrelated brain activity (Pizzagalli et. al, 2009), while bipolar disorder is associated with elevated
reward-related brain activity (Nusslock et. al, 2012). In addition to fMRI, researchers also use
event-related potentials (ERP) to investigate the biology of mood disorders. ERPs measure
neural activity that occurs during cognitive and emotional processing. They are non-invasive and
offer excellent temporal resolution, enabling researchers to examine neurophysiological activity
milliseconds after the onset of a stimulus (Foti and Hajcak, 2010). Previous research has linked
mood-related symptoms to a specific ERP response during a reward-based gambling task. For
example, Foti and Hajcak (2009) asked participants to pick between two doors presented on a
computer screen, one of which concealed a prize and one of which concealed a negative
outcome. Using ERP, they found a specific neurophysiological waveform that peaked at
approximately 300 milliseconds after a participant received negative but not positive feedback.
This response, called feedback related negativity (FN), has been identified as a typical pattern of
neural activity for negative feedback (Foti and Hajcak, 2010). This pattern is now presumed to
be an indicator of reward sensitivity (Cohen, Elger, and Ranganath, 2007). Foti and Hajcak
(2009) found that depressive symptoms predicted smaller FN magnitude, suggesting that FN
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could be a biomarker of depression. However, while FN has been investigated in relation to
depressive symptoms, the relationship between FN and bipolar symptoms has yet to be explored.
In the proposed study, we seek to investigate for the first time the relationship between
profiles of FN magnitude and bipolar symptomatology. Past research with FN has shown the link
between low reward sensitivity and depressive symptoms, but the high reward sensitivity
associated with bipolar symptoms has not yet been supported by a positive correlation between
elevated bipolar symptoms and the magnitude of FN that we predict in this study. Participants
will be 10-15 Northwestern University undergraduates recruited from the Introduction to
Psychology summer course or via flyers for payment. Participants will receive $10 per hour plus
up to an additional $5 based on task performance from the URG and funds available in Professor
NusslockÕs laboratory. Participants will be asked to complete the Mood Spectrum-Self ReportLifetime (MOOD_SR_L) in order to assess subsyndromal bipolar symptoms (Fagiolini et. al,
1999). Previous research in Professor NusslockÕs Mood Disorders Lab has demonstrated
meaningful variability in subsyndromal bipolar symptoms in Northwestern Undergraduates using
the MOOD_SR_L. ERP will be recorded during the reward-gambling task used in Foti and
Hajcak (2010). Participants will pick between two doors and either gain 50 cents or lose 25
cents. The loss condition, which will elicit an FN response, will occur exactly half the time
throughout 40 trials. ERP data will be processed and analyzed using Neuroscan software in
Professor NusslockÕs laboratory and the relationship between bipolar symptoms and FN
magnitude will be analyzed using bivariate correlation and multiple regressions in SPSS (a
statistical computer program). Results will be considered significant if p value <0.05.
The summer will provide sufficient time for me to practice leading the administration of
EEG, set up the gambling task in E-Prime (program that runs tasks), pilot the task, and test 10-15
participants. For my senior honors thesis, I hope to continue the study into the academic year
ultimately testing 40-50 participants. This work would allow insight into individual differences
in abnormal reward-processing associated with bipolar symptoms. In addition, it may aid the
identification of a novel biomarker for differentiating between unipolar depression and bipolar
disorder and lead to improved diagnosis and treatment for bipolar disorder.
My research experience and coursework has prepared and inspired me to complete an
independent project in Professor NusslockÕs Mood Disorders Laboratory. My prior experience
conducting ERP studies and processing ERP-related data in this lab will allow me to complete
the proposed study. In addition, I have practiced administering behavioral tasks, coding, scoring,
and organizing data using Excel, and gained data analysis experience by working at the Oxford
University Attention, Brain, and Cognitive Development Lab and an NIMH panic disorder study
at Weill Cornell Medical Center. While studying abroad at Oxford, Psychological Disorders,
Cognitive Neuroscience, and Behavioral Neuroscience courses informed my understanding of
mood disorders and neurobiological research approaches relevant to this study. Finally, I have
become familiar with the statistical methods necessary for this project through Statistics and
Research Methods classes. Professor NusslockÕs Lab will provide me with the faculty support
and resources I need in order to complete an independent summer project.
Using the URG, I would further explore my passion for mood disorders research, expand
work I complete this summer into a meaningful senior honors thesis, and prepare for graduate
study in clinical psychology. I would like to pursue a PhD to investigate neurobiological and
cognitive models of mood disorders or anxiety that may lead to more effective and widely
accessible treatments. The URG would provide invaluable experience, helping me to develop
into an independent researcher and pursue a career in research.
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References
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