BOLD Variability is Related to Dopaminergic Neurotransmission and Cognitive Aging.
Dopamine (DA) losses are associated with various aging-related cognitive deficits. Typically, higher moment-to-moment brain signal variability in large-scale patterns of voxels in neocortical regions is linked to better cognitive performance and younger adult age, yet the physiological mechanisms regulating brain signal variability are unknown. We explored the relationship among adult age, DA availability, and blood oxygen level-dependent (BOLD) signal variability, while younger and older participants performed a spatial working memory (SWM) task. We quantified striatal and extrastriatal DA D1 receptor density with [(11)C]SCH23390 and positron emission tomography in all participants. We found that BOLD variability in a neocortical region was negatively related to age and positively related to SWM performance. In contrast, BOLD variability in subcortical regions and bilateral hippocampus was positively related to age and slower responses, and negatively related to D1 density in caudate and dorsolateral prefrontal cortex. Furthermore, BOLD variability in neocortical regions was positively associated with task-related disengagement of the default-mode network, a network whose activation needs to be suppressed for efficient SWM processing. Our results show that age-related DA losses contribute to changes in brain signal variability in subcortical regions and suggest a potential mechanism, by which neocortical BOLD variability supports cognitive performance.
Aging Research Center, Karolinska Institute, SE-113 30 Stockholm, Sweden.|Wellcome Trust Center for Neuroimaging, University College London, WC1N 3BG London, UK.
Marc
M
Guitart-Masip
Aging Research Center, Karolinska Institute, SE-113 30 Stockholm, Sweden.|Umeå Center for Functional Brain Imaging, S-90187 Umeå, Sweden.
Alireza
A
Salami
Max Plank Institute for Human Development, 14195 Berlin, Germany.
Douglas
D
Garrett
Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
Anna
A
Rieckmann
Max Plank Institute for Human Development, 14195 Berlin, Germany.
Ulman
U
Lindenberger
Aging Research Center, Karolinska Institute, SE-113 30 Stockholm, Sweden.
Lars
L
Bäckman
D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology*; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology; D000066492:Cognitive Aging; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D065852:Spatial Memory / Q000502:physiology; D055815:Young Adult
D017447:Receptors, Dopamine D1; D010100:Oxygen
BOLD variability; cognitive aging; default mode network; dopamine; spatial working memory