Neuromodulation and aging: implications of aging neuronal gain control on cognition

• Dopamine modulation declines in various brain regions during aging.
• A computational role of dopamine is neuronal gain control.
• Aging neuronal gain control attenuates processing fidelity and distinctiveness.
• Impaired dopamine modulation in aging affects brain and cognitive functions.
• Cognitive training and brain stimulation are promising avenues for future aging research.

The efficacy of various transmitter systems declines with advancing age. Of particular interest, various pre-synaptic and post-synaptic components of the dopaminergic system change across the human lifespan; impairments in these components play important roles in cognitive deficits commonly observed in the elderly. Here, we review evidence from recent multimodal neuroimaging, pharmacological and genetic studies that have provided new insights for the associations among dopamine functions, aging, functional brain activations and behavioral performance across key cognitive functions, ranging from working memory and episodic memory to goal-directed learning and decision making. Specifically, we discuss these empirical findings in the context of an established neurocomputational theory of aging neuronal gain control. We also highlight gaps in the current understanding of dopamine neuromodulation and aging brain functions and suggest avenues for future research.