Dopamine DRD2 polymorphism alters reversal learning and associated neural activity

Area of Science:

• Neuroscience
• Genetics
• Cognitive Psychology

Background:

• The DRD2/ANKK1-TaqIa polymorphism's A1 allele is linked to lower dopamine D2 receptor expression in the striatum.
• A1 allele carriers have previously shown difficulties with learning from negative feedback.

Purpose of the Study:

• To investigate the effects of the DRD2/ANKK1-TaqIa polymorphism on reversal learning using functional MRI (fMRI).
• To explore the neural mechanisms underlying impaired feedback processing in A1 allele carriers.

Main Methods:

• Functional magnetic resonance imaging (fMRI) was employed to study participants performing a probabilistic reversal learning task.
• Participants were genotyped for the DRD2/ANKK1-TaqIa polymorphism, categorizing them as A1 allele carriers (A1+) or non-carriers.

Main Results:

• A1+ subjects demonstrated subtle deficits in reversal learning, including difficulty sustaining rewarded responses post-reversal and a reduced tendency to persist with rewarded choices.
• Both groups showed heightened fMRI responses to negative feedback in the rostral cingulate zone (RCZ) and anterior insula.
• Negative feedback triggering behavioral change activated the ventral striatum and midbrain dopaminergic areas.
• A1+ individuals lacked a graded RCZ response to sequential negative feedback and showed reduced activation in the right ventral striatum and right lateral orbitofrontal cortex (lOFC) during reversals.

Conclusions:

• A genetically determined reduction in dopamine D2 receptors impairs feedback integration in the RCZ.
• This neural deficit is associated with diminished recruitment of the ventral striatum and lOFC during reversal learning.
• These findings elucidate the neurobiological basis for behavioral differences observed in individuals with the A1 allele.