Neurophysiological correlates of age-related changes in working memory updating.
Normal aging is associated with a gradual decline in executive functions such as set-shifting, inhibition, and updating, along with a progressive decline of neurotransmitter systems including the dopamine system. Modulation from the dopamine system is thought to be critical for the gating of information during working memory. Given the known relationships between executive aging, cognition, and dopamine, this study aims to explore the neurobiology underlying age-related changes in working memory updating using fMRI with healthy subjects from across the adult age spectrum. Our results indicate that older age is associated with poorer performance, reduced meso-cortico-striatal activation, and reduced functional coupling between the caudate and the VLPFC during the updating task. Additionally, caudate activation is associated with improved accuracy and VLPFC activation with faster reaction times in the full sample. Thus, older subjects' under-recruitment of and reduced functional coupling between these regions may specifically underlie age-related changes in working memory updating. These results are consistent with computational models of executive cognition and dopamine-mediated age-related cognitive decline.
Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA.
Jamie E
JE
Podell
Fabio
F
Sambataro
Vishnu P
VP
Murty
Matthew R
MR
Emery
Yunxia
Y
Tong
Saumitra
S
Das
Terry E
TE
Goldberg
Daniel R
DR
Weinberger
Venkata S
VS
Mattay
D000328:Adult; D000375:Aging / Q000502:physiology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D009434:Neural Pathways / Q000503:physiopathology*