abstract Article history:Received 4 March 2011Revised 1 August 2011Accepted 11 August 2011Available online xxxxKeywords:Dynamic causal modelling (DCM)Associative emotional learningDopamineGeneticsDARPP-32Effective connectivity Associative emotional learning, which is important for the social emotional functioning of individuals and isoften impaired in psychiatric illnesses, is in part mediated by dopamine and glutamate pathways in the brain.The protein DARPP-32 is involved in the regulation of dopaminergic and glutaminergic signaling. Conse-quently, it has been suggested that the haplotypic variants of the gene PPP1R1B that encodes DARPP-32are associated with working memory and emotion processing.We hypothesized that PPP1R1B should have a signiﬁcant inﬂuence on the network of brain regions involvedin associative emotional learning that are rich in DARPP-32, namely the striatum, prefrontal cortex (compris-ing the medial frontal gyrus and inferior frontal gyrus (IFG)), amygdala and parahippocampal gyrus (PHG).Dynamic causal models were applied to functional MRI data to investigate how brain connectivity duringan associative emotional learning task is affected by different single-nucleotide polymorphisms (SNPs) ofPPP1R1B: rs879606, rs907094 and rs3764352.Compared to heterozygotes, homozygotes with GTA alleles displayed increased intrinsic connectivity be-tween the IFG and PHG, as well as increased excitability of the PHG for negative emotional stimuli. Wehave also elucidated the directionality of these genetic inﬂuences. Our data suggest that homozygotes withGTA alleles involve stronger functional connections between brain areas in order to maintain activation ofthese regions. Homozygotes might engage a greater degree of motivational learning and integration of infor-mation to perform the emotional learning task correctly.We conclude that PPP1R1B is associated with the neural network involved in associative emotional learning.© 2011 Elsevier Inc. All rights reserved.
['Branislava Ćurčić-Blake', 'Marte Swart', 'Gert J. Ter Horst', 'Dave R. M. Langers', 'Ido P. Kema', 'André Aleman']
Variation of the gene coding for DARPP-32 (PPP1R1B) and brain connectivity during associative emotional learning