CBF gradient and excitatory-inhibitory balance measured from pre-SMA – importance in aging and semantic fluency task difficulties

In this report, we aim to systematically investigate the neural changes related to healthy aging in the presupplementary motor area (pre-SMA) and how these changes are associated with the semantic fluency task difficulty. We quantified a spatial cerebral blood flow (CBF) gradient based on previously identified task-specific subregions of the pre-SMA using pseudo-Continuous Arterial Spin Labeling, and we assessed the excitatory-inhibitory balance (EIB) using the ratio of gamma-aminobutyric acid (GABA+) to glutamate and glutamine complex (Glx) using magnetic resonance spectroscopy. We identified an ascending gradient in CBF from anterior to posterior among younger participants, which was absent in older participants. We interpret this loss of the CBF gradient in the context of neural dedifferentiation. There was a notable difference in tissue-corrected EIB between younger and older participants. Older participants exhibited a stronger inhibitory tone in the pre-SMA, driven by reduced tissue-corrected Glx in the older cohort. We interpret the increased EIB as a potential marker of under- or over-compensated synaptic scaling. Additionally, we found no relationship between neural dedifferentiation, as indicated by the CBF gradient, and synaptic scaling (EIB), suggesting that these are two distinct processes related to age-related neural changes. The tissue-corrected EIB exhibited a positive relationship with the difficulty of the semantic fluency task. However, we found no correlation between behavior and the CBF gradient. Our findings indicate that the inhibitory tone and synaptic scaling in the pre-SMA, rather than the CBF gradient and neural dedifferentiation, are crucial for managing the challenges posed by the semantic fluency task.