Neural substrates of letter fluency processing in young adults who were born very preterm: alterations in frontal and striatal regions.

Several studies have described poorer performance in executive-type tasks in individuals who were born very preterm compared to controls. As there is evidence that high-order executive functions may be underpinned by neuronal activity in frontal-striatal circuits, we investigated with functional MRI a group of young adults who were born very preterm (n=28, gestational age <33 weeks) and controls (n=26) in order to detect possible alterations in brain activation during completion of a letter fluency task with differential cognitive loading ("easy" and "hard" letter trials). Structural MRI data were also collected to clarify whether any functional changes were associated with structural brain volume changes. Group membership, level of task difficulty and gestational age had significant effects on brain activation. In the absence of significant between-group differences in task performance, during "easy" letter trials, very preterm-born individuals showed attenuated activation in anterior cingulate gyrus, right caudate nucleus and left inferior frontal gyrus compared to controls. During "hard" letter trials, very preterm-born individuals showed both decreased and increased BOLD signal compared to controls, in left middle frontal and anterior cingulate gyrus, respectively. BOLD signal in caudate nucleus and anterior cingulate gyrus, in regions with peaks close to areas where between-group differences were observed, was linearly associated with gestational age. Analysis of structural MRI data showed altered grey matter distribution in the preterm-born group compared to controls. However, fMRI results were only partly explained by structural changes, and may reflect processes of functional plasticity for the successful completion of executive-type operations.