Abnormal Reward System Activation in Mania

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Abnormal Reward System Activation in Mania

• Jalene Lanter MS3 UIC

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Background

• Manic patients are often characterized by
  abnormal goal pursuit, elevated levels of
  achievement motivation and drive.
• May be caused by dysregulation of neural networks
  for motivation and goal directed behavior
• Support 2005 Gorrindo et al study

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Brain Areas Studied

• Mesolimbic dopaminergic system
• Ventral tegmental area (mesencephalon) origin
  for mesolimbic and mesocortical dopamine paths
• Nucleus accumbens (telencephalon) part of the
  basal ganglia, connection to limbic system

Picture NIH NIDA
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Why were these areas studied?

• Clear link between reward and mesolimbic
  dopaminergic system activation
• Effectiveness of anti-psychotic drugs for
  treatment of acute mania (dopamine antagonists)
• Few fMRI studies of reward networks in bipolar

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Hypotheses

• (1) Medicated bipolar patients during an acute
  manic episode will show deficient reward
  processing in the form of decreased
  reward-related brain activation.
• (2) Medicated patients during an acute episode
  of schizophrenia will not show similarly
  decreased reward-related, which provides evidence
  that anticipated changes in medicated, manic
  patients are not due to neuroleptic medication
  or acute psychiatric illness

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Study Design

• Subjects (Table 1 article)
• 12 healthy control patients
• 12 acutely manic/mixed episode patients, PmHx
  Bipolar I disorder (medicated, psychosis in 9 of
  12)
• 12 acutely schizophrenic or schizoaffective
  patients (medicated)
• Diagnosis of these disorders utilized SCID by a
  non involved psychiatrist
• Medication varied

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Reward task

• Monetary incentive task
• 3 levels of reward - 1.25, 0.04, 0
• Chance of winning same regardless of reaction
  time
• 60 trials, correct response win
• 40 trials, correct/incorrect response no win
  (omission)
• Random order
• Loss of 1 if no response was provided

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fMRI acquisition and analysis

• 3 Tesla MRI
• T1 anatomical images
• fMRI images T2, BOLD contrast changes
• Images in the basal region of the brain - basal
  ganglia, orbitofrontal region, ventral frontal
  region
• Statistical analysis entire study effects,
  within the group effects, between the group
  differences
• Each subject had an fMRI signal time series
  created for regions studied

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Results accuracy and reaction time
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Results fMRI data

• Phase 1 Expectation
• High vs. Low reward (1) activation nucleus
  accumbens, ventral tegmental area, anterior
  insula, parahippocampus, cingulate, medial
  prefrontal cortex
• High vs. No reward (2) activation anterior
  insula/inferior frontal gyrus, brain stem
• Phase 2 Outcome
• Win vs. Omission (3) activation nucleus
  accumbens, cingulate and medial prefrontal
  cortex, right parahippocampus
• Omission vs. Win (4)

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fMRI data contd

• Control patients activation occurred for all
  the contrasted trials
• Schizophrenic patients similar activation
  pattern to control subjects
• Manic patients no activation of reward
  circuitry
• Significantly more activation in left nucleus
  accumbens in controls vs. bipolar patients,
  particularly during the outcome phase
• Similar activation of ventral tegmental area
  during expectation phase
• Differences between the signal for receipt vs.
  omission of reward were greater in schizophrenic
  patients and healthy controls as compared to
  bipolar patients

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Nucleus accumbens activation differential
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Discussion Evidence of altered reward
processing in bipolar patients

• Expectation Phase
• No significant differences between groups for
  activation bipolar patients had high levels of
  activation for all trials
• Significantly, no decreased reaction time for
  trials with high reward in bipolar patients
  (previous graph)
• All stimuli were equally salient to the bipolar
  patients eliciting high fMRI signals in all
  conditions irrespective of the reward to be
  expected
• Outcome Phase
• Bipolar patients did not have decreased fMRI
  signals in the nucleus accumbens during omission
  trials as compared to healthy controls and
  schizophrenic patients
• Correlates to previous findings about bipolar
  patient decision making skills

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Discussion contd

• PET scan during Cambridge Decision Making Task
• Bipolar patients showed abnormal activation in
• Dorsal anterior cingulate
• Frontal polar region
• Right inferior frontal cortical region
• Anterior cingulate activation predicted severity
  of manic symptoms
• Cognitive/emotional tasks
• Reinforcement of learning

Picture Nih.gov
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Discussion alteration in cognitive processing

• Specific cognitive deficits are seen in manic
  patients
• Early information processing
• Decision making
• Response inhibition
• Sustained attention

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Limitations

• All patient were medicated with anti-psychotics
  influence on dopaminergic system
• Medication regimens were not standard
• Effects of anti-psychotics in healthy controls
• Small number of subjects limits generalizability
• History of illegal drug use, cigarette smoking in
  some patients

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Conclusion

• Initial evidence for dysfunction in the reward
  pathways in acutely manic patients
• Specifically prediction error signals ventral
  striatum
• ? Neural basis for deficits in learning and
  decision making in manic patients

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• Reference
• Abler et al. Abnormal reward system activation in
  mania. Neuropsychopharmacology. 2008 August
  33(9) 2217-2227.