Prefrontal-Hippocampal Coupling During Memory Processing Is Modulated by COMT Val158Met Genotype

Alessandro Bertolino, Valeria Rubino, Fabio Sambataro, Giuseppe Blasi, Valeria Latorre, Leonardo Fazio, Grazia Caforio, Vittoria Petruzzella, Bhaskar Kolachana, Ahmad Hariri, Andreas Meyer-Lindenberg, Marcello Nardini, Daniel R. Weinberger, Tommaso Scarabino

Research output: Contribution to journalArticlepeer-review

144 Scopus citations


Background: Studies in humans and in animals have demonstrated that a network of brain regions is involved in performance of declarative and recognition memory tasks. This network includes the hippocampal formation (HF) as well as the ventrolateral prefrontal cortex (VLPFC). Studies in animals have suggested that the relationship between these brain regions is strongly modulated by dopamine. Methods: Using fMRI in healthy humans matched for a series of demographic and genetic variables, we studied the effect of the COMT val158met polymorphism on function of HF and VLPFC as well as on their functional coupling during recognition memory. Results: The COMT Val allele was associated with: relatively poorer performance at retrieval; reduced recruitment of neuronal resources in HF and increased recruitment in VLPFC during both encoding and retrieval; and unfavorable functional coupling between these two regions at retrieval. Moreover, functional coupling during retrieval was predictive of behavioral accuracy. Conclusions: These results shed new light on individual differences in responsivity and connectivity between HF and VLPFC related to genetic modulation of dopamine, a mechanism accounting at least in part for individual differences in recognition memory performance.

Original languageEnglish (US)
Pages (from-to)1250-1258
Number of pages9
JournalBiological psychiatry
Issue number11
StatePublished - Dec 1 2006
Externally publishedYes


  • COMT val158met
  • connectivity
  • declarative memory
  • dopamine
  • hippocampus
  • prefrontal cortex

ASJC Scopus subject areas

  • Biological Psychiatry


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