Elsevier

Current Opinion in Neurobiology

Volume 29, December 2014, Pages 148-158
Current Opinion in Neurobiology

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

https://doi.org/10.1016/j.conb.2014.07.009Get rights and content

Highlights

  • 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.

Section snippets

Global aging

According to the United Nation's 2011 report on world population prospects, the number of people aged 65 or older will outnumber children under age 5 before 2020 [1]. This unprecedented demographic shift is jointly driven by reduced fertility rates and an increase in life expectancy. In most developed countries the average life expectancy at birth has increased from about 45 years in 1840 to above 75 years in 2000 [2, 3]. This remarkable 30-year gain in physical health is, however, not

Aging-related declines of neurotransmitter systems

Neurons contain and release a large number of neurotransmitters, which regulate signal transmissions between neurons [5]. Several transmitter systems, such as the catecholamines  dopamine, serotonin, and norepinephrine  and acetylcholine, originate from the brain stem (e.g. subtantia nigra, ventral tegmental area, raphe nucleus) and broadly innervate various neural circuitries throughout the brain. In contrast to faster transient effects on local synaptic neurotransmission, these transmitter

Aging neuronal gain control

Over the past two decades, computational neuroscience has contributed to understanding the mechanisms through which dopamine [24, 25, 26, 27], serotonin [28], norepinephrine [29] and acetylcholine [30] regulate the dynamics of neural information propagation within and between brain circuitries. The roles of neuromodulators have been modeled at different levels of analysis as well as with respect to different functionalities (e.g. attention, memory as well as reward and affective processing).

Aging of information processing fidelity

At the behavioral level, information processing fidelity can be indexed by the inverse of within-person trial-to-trial reaction time (RT) variability. Higher levels of within-person behavioral variability when performing sensorimotor, perceptual, and cognitive tasks reflect a lack of processing fidelity and is indicative of suboptimal processing associated with pathology or aging [38]. Across the lifespan, information processing fidelity increases substantially during childhood in a various

Aging of memory functions

In his autobiography (1924, Haper & Brothers Publishers), Mark Twain wrote about his memory problems at old age: “When I was younger, I could remember anything, whether it had happened or not; but my faculties are decaying now and soon I shall be so that I cannot remember any but the things that never happened.” Twain's personal lamentation voiced a core issue of human conditions that most people experience with advancing age: the problem of less reliable memory. Aging-related declines in the

Aging of goal-directed learning and decision-making

Midbrain dopamine neurons are critically involved in modulating reward processing [76]. Reward anticipation has been shown to enhance long-term memory formation through stronger coupling between the striatal and hippocampal activities during encoding [77]. Thus, interactions between striatal dopamine release and hippocampal memory processes may, on the one hand, bias memory for events with higher reward or motivational significance and, on the other hand, provide a mean for forming integrated

Outlook: enhancing neuronal gain control via cognitive training and non-invasive brain stimulation

If reduced neuronal gain control is at the heart of dopamine-related cognitive decline in aging, how could neuronal gain control be enhanced in older adults? In the future, pharmacological intervention might be a viable approach for restoring neuromodulatory functions in regulating the processing fidelity of synaptic signal transmission or gating information transfers between cortical networks. To date, however, cognitive enhancer drugs that are suitable for the non-clinical elderly populations

Conclusions

Computational models have suggested that suboptimal dopamine modulation attenuates neuronal gain control, which yields a sequence of suboptimal neurocompuational effects that (Figure 2) may underlie deficits in older adults’ cognition and behavior across multiple domains. Over the last decade, neuroimaging, genetic and pharmacological manipulation studies have accumulated and provided compelling evidence for a link between deficient dopamine modulation in the aging brain and the elderly's

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

Shu-Chen Li's research has been supported by fundings from the Max Planck Society (1996–2012), German Science Foundation (DFG LI 878/12-2), and the Ministry for Education and Research (BMBF 0Q0913, 01GQ1313). She gives special thanks to all collaborators in the Neuromodulation of Lifespan Cognition Project, which was sponsored by the Max Planck Institute for Human Development (2005–2012; M.FE.A.BILD0005). Anna Rieckmann was supported by a Marie Curie International Outgoing Fellowship from the

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