Prefrontal Cortex and Reward

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Prefrontal Cortex and Reward

• Chai Bishop
• 5/3

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Pathological Gambling is Linked to Reduced
Activation of the Mesolimbic Reward SystemJan
Reuter, thomas Raedler, Michael Rose, Iver hand,
Jan Glascher, christian Buchel

• Pathological gambling
• -defined as gambling that interferes with
  interpersonal relationships and negatively
  affects financial and socioeconomic status
• -a common disorder with a prevalence of 1.6 in
  adults

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Premise of study

• Linkage between Drug Addiction and Pathological
  Gambling
• -symptoms
• -mesolimbic reward system
• -drug self administration experiments
• By analogy to drug addiction, it has been
  speculated that pathological gambling might also
  be related to a deficiency of the mesolimbic
  dopaminergic reward system

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Methods-Using fMRI imaging and a
guessing task known to robustly activate the
ventral striatum (Knutson, Delgado)- the
experimenters studied 12 pathological gamblers
(assessed with a questionnaire) and 12 closely
matched healthy controls
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ResultsFig.1-there was significantly greater
activity during winning than during losing in the
ventral striatum which served as verification
that the task robustly activated the ventral
striatum-fewer voxels (volume pixel, smallest
distinguishable boxed shaped part of a 3D image)
were activated in pathological gamblers than in
controls-only the controls showed additional
activation in the ventromedial and ventrolateral
prefrontal cortex (VMPFC) (fig. 1c)
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Fig.2-direct comparison of both groups showed
significantly lower activation of the right
ventral striatum in pathological gamblers than in
controls (fig 2b)-pathological gamblers showed
significantly weaker activation in the VMPFC (fig
2c)
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Additional data-Regression
analysis to correlate signal changes in the
ventral striatum with the severity of gambling in
each patient showed that the severity of gambling
in pathological gamblers showed a significant
negative correlation w/ the response in the right
ventral striatum (r -0.53) and the response in
the VMPFC (r -.53) (fig 2a,d)-To ensure this
result was not related to depression or smoking
habits in some pathological gamblers 2 additional
analyses were performed 1. A categorical
analysis comparing non-depressed pathological
gamblers to a smaller control group perfectly
matched for smoking that showed the same
pattern 2. A correlation analysis w/o the
depressed patients that confirmed the initial
data and actually showed an even stronger
relationship between gambling severity and
hypoactivation of the right ventral striatum (r
-0.88) and VMPFC (r -0.67)
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Conclusion

• -through studying pathological gamblers and
  controls during a guessing game using fMRI, the
  experimenters observed a reduction of ventral
  striatal and ventromedial prefrontal activation
  in the pathological gamblers that was negatively
  correlated with gambling severely linking
  hypoactivation of these areas to disease severity
  which may represent the neural basis for impaired
  impulse control in pathological gamblers.
• - amongst pathological gamblers natural enforcers
  are not strong enough for dopamine to reach and
  maintain a homeostatic baseline level.

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II. Prediction Error for Free Monetary Reward in
the Human Prefrontal CortexN. Ramnani, R.
Elliot, B.S Athwal, and R.E. Passingham

• Premise of the study
• -The execution of goal-directed behavior is
  always followed by monitoring for the successful
  achievement of the goal. For this process to work
  effectively, a representation of the expected
  goal must be compared with the outcome.
• -Midbrain dopamine systems of the primate brain
  send projections to the basal ganglia and
  widespread regions of the frontal lobes
  (Ghashghaei and Barbas). These routes are
  important for conveying reward-related
  information to frontostriatal circuitry involved
  in cognitive processing-the firing
  characteristics of dopamine neurons are
  determined by the ability of animals to predict
  rewards in advance of their occurrence and
  whether the predictions about outcomes are
  violated or verified.

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Primary Aim-to localize regions of the human
brain that were responsive to violations of
expectations related to freely delivered monetary
rewards

• Methods
• -event related fMRI in 6 human subjects to
  examine activity related to the failure of
  expected rewards and the occurrence of unexpected
  rewards, where outcomes were not contingent on
  any behavior
• --An earlier study Ramnani and Miall (2003) used
  the same exact conditioned stimuli and reported
  that when conditioned stimuli predict reward
  activity is found in the ventral pallidum on the
  basis of that study Ramnani et al. used a region
  of interest approach to test for the possibility
  that one could predict activity in the same
  region in this study for conditioned stimuli that
  predict rewards compared w/conditioned stimuli
  that predict nonrewards, even if the outcomes are
  as predicted

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Results

• Fig 2.
• -prediction errors evoke activity in 2 separate
  frontotemporal networks, the anterior prefrontal
  cortex (a medial part of the orbitofrontal
  cortex) and in lateral parts of the dorsal
  prefrontal cortex (Table 2, fig. 2B),
• -unexpected rewards evoked phasic event related
  decreases in the anterior prefrontal cortex and
  parahippocampal gyrus in most subjects but
  increases in the inferior frontal sulcus and
  cerebellar cortex

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Fig 3.-This study found high activations within
its region of interest, the ventral striatum
which supports their conclusion that conditioned
stimuli that predict monetary reward cause
activity changes in the basal ganglia.
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Conclusion

• -Projections between orbital and polar areas of
  the prefrontal cortex and areas of the temporal
  lobes found in primates (Barbas et al.) represent
  important connections that enable visual
  information from the temporal lobe object
  processing pathways to reach the prefrontal
  cortex, nearly all fibers that connect the
  temporal pole with the prefrontal cortex pass
  through the uncinate fascicle (Ungerleider)
• -The ability to form specific object-rewards
  associations was severely impaired after uncinate
  fascicle lesions (Parker and Gaffan)
• -This study has demonstrated that violations of
  predictions made on the basis of such
  associations specifically cause activity changes
  in frontotemporal circuitry.
• -Due to the experimental design Ramnani et al.
  were able to separately determine activity
  changes related to unexpected rewards and
  unexpected failures of reward in reversal trials,
  changes were found in the anterior prefrontal
  cortex for both types of prediction error but the
  medial part of the orbitofrontal cortex shows
  activity changes that are specific to the
  presentation of unexpected reward
• -The results are consistent with the view that
  changes in activity in frontotemporal circuits do
  not simply represent the processing of predictive
  stimuli and rewards but actively encode the
  associations between them
• Lesions may therefore impair learning because
  frontotemporal circuitry is required for the
  processing of error feedback

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III. Separate Neural systems Value Immediate
Delayed Monetary RewardsSamuel M. McClure,
David I. Laibson, George Loewenstein, Jonathan D.
Cohen

• Premise
• -Human decision makers are apparently torn
  between impulsiveness and patience
• -consumers behave impatiently today but
  prefer/plan to act patiently in the future
• Ex. Someone offered the choice between 10
  today and 11 tomorrow might be tempted to choose
  the immediate option. However, if asked today to
  choose between 10 in a year and 11 in a year
  and a day, the same person is likely to prefer
  the slightly delayed but larger amount.
• Hypothesis
• -The discrepancy between short-run and long run
  preferences reflects the differential activation
  of distinguishable neural systems.
• - ß , short run impatience is driven by the
  limbic system, which responds preferentially to
  immediate rewards and is less sensitive to the
  value of future rewards
• - d , long run patience is mediated by the
  lateral prefrontal cortex and associated
  structures, which are able to evaluate tradeoffs
  between abstract rewards, including rewards in
  the more distant future
• Based on a time discounting function referred to
  as beta-delta preference (Pollack)

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Methodsparticipants made a series of binary
choices between smaller/earlier and larger/later
monetary amounts while their brains were scanned
using fMRIspecific amounts ranging from 5-40
and times of availability ranging from the day of
the experiment to 6 weeks later
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ResultsFig. 1-brain areas disproportionately
activated by choices involving an immediate
outcome (ß areas) include the ventral striatum,
medial orbitoprefrontal cortex, and medial
prefrontal cortex. As predicted these are the
classic limbic structures and closely related
paralimbic cortical projections
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Fig.2-voxels that loaded on all decisions
variable are d areas, these were not activated by
all decision epochs and were not preferentially
activated by experimental choices that included
an option for a reward today, areas of the LPFC
as predicted
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Conclusions

• -When humans are offered the choice between
  rewards available at different points in time,
  the relative values of the options are discounted
  according to their expected delays until delivery
• -2 separate systems are involved in such
  decisions
• 1. Parts of the limbic system (associated with
  the midbrain dopamine system including paralimbic
  cortex) are preferentially activated by decisions
  involving immediately available rewards, ß
• 2. Regions of the lateral prefrontal cortex and
  posterior parietal cortex are engaged uniformly
  by intertemporal choices irrespective of delay, d
• -this analysis shows that the degree of
  engagement of the these areas is consistent with
  a key role in future planning

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Overall Conclusions on PFC and Reward

• PFC plays an important role in
• I. Gambling negative correlation between PFC
  activation and addiction severity, implicating
  that it is not a choice
• II. Prediction Error predictions based on
  monetary reward irrespective of behavior,
  implicates PFC in stimuli association processes
• III. Decisions based on monetary reward
  irrespective of delay, future planning skills