Age-related and genetic modulation of frontal cortex efficiency

J Cogn Neurosci. 2014 Apr;26(4):746-54. doi: 10.1162/jocn_a_00521. Epub 2013 Nov 18.


The dorsolateral pFC (DLPFC) is a key region for working memory. It has been proposed that the DLPFC is dynamically recruited depending on task demands. By this view, high DLPFC recruitment for low-demanding tasks along with weak DLPFC upregulation at higher task demands reflects low efficiency. Here, the fMRI BOLD signal during working memory maintenance and manipulation was examined in relation to aging and catechol-O-methyltransferase (COMT) Val(158)Met status in a large representative sample (n = 287). The efficiency hypothesis predicts a weaker DLPFC response during manipulation, along with a stronger response during maintenance for older adults and COMT Val carriers compared with younger adults and COMT Met carriers. Consistent with the hypothesis, younger adults and met carriers showed maximal DLPFC BOLD response during manipulation, whereas older adults and val carriers displayed elevated DLPFC responses during the less demanding maintenance condition. The observed inverted relations support a link between dopamine and DLPFC efficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging* / genetics
  • Brain Mapping
  • Catechol O-Methyltransferase / genetics*
  • Education
  • Female
  • Frontal Lobe / physiology*
  • Genotype
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory, Short-Term / physiology*
  • Middle Aged
  • Neuropsychological Tests
  • Polymorphism, Genetic
  • Prefrontal Cortex / physiology
  • Task Performance and Analysis


  • Catechol O-Methyltransferase