Cognitive neuroscience of the healthy aging human brain has thus far addressed age-related changes of local functional and structural properties of gray and white matter and their association with declining or preserved cognitive functions. In addition to these localized changes, recent neuroimaging research has attributed an important role to neural networks with a stronger focus on interacting rather than isolated brain regions. The analysis of functional connectivity encompasses task-dependent and -independent synchronous activity in the brain, and thus reflects the organization of the brain in distinct performance-relevant networks. Structural connectivity in white matter pathways, representing the integrity of anatomical connections, underlies the communication between the nodes of these functional networks. Both functional and structural connectivity within these networks have been demonstrated to change with aging, and to have different predictive values for cognitive abilities in older compared to young adults. Structural degeneration has been found in the entire cerebral white matter with greatest deterioration in frontal areas, affecting whole brain structural network efficiency. With regard to functional connectivity, both higher and lower functional coupling has been observed in the aging compared to the young brain. Here, high connectivity within the nodes of specific functional networks on the one hand, and low connectivity to regions outside this network on the other hand, were associated with preserved cognitive functions in aging in most cases. For example, in the language domain, connections between left-hemisphere language-related prefrontal, posterior temporal and parietal areas were described as beneficial, whereas connections between the left and right hemisphere were detrimental for language task performance. Of note, interactions between structural and functional network properties may change in the course of aging and differentially impact behavioral performance in older versus young adults. Finally, studies using noninvasive brain stimulation techniques like transcranial direct current stimulation (tDCS) to simultaneously modulate behavior and functional connectivity support the importance of ‘selective connectivity' of aging brain networks for preserved cognitive functions. These studies demonstrate that enhancing task performance by tDCS is paralleled by increased connectivity within functional networks. In this review, we outline the network perspective on healthy brain aging and discuss recent developments in this field.

1.
Park DC, Reuter-Lorenz P: The adaptive brain: aging and neurocognitive scaffolding. Annu Rev Psychol 2009;60:173-196.
2.
Grady C: The cognitive neuroscience of ageing. Nat Rev Neurosci 2012;13:491-505.
3.
Davis SW, Dennis NA, Daselaar SM, Fleck MS, Cabeza R: Que pasa? The posterior-anterior shift in aging. Cereb Cortex 2008;18:1201-1209.
4.
Andrews-Hanna JR, Snyder AZ, Vincent JL, Lustig C, Head D, Raichle ME, Buckner RL: Disruption of large-scale brain systems in advanced aging. Neuron 2007;56:924-935.
5.
Meunier D, Achard S, Morcom A, Bullmore E: Age-related changes in modular organization of human brain functional networks. Neuroimage 2009;44:715-723.
6.
Wen W, Zhu W, He Y, Kochan NA, Reppermund S, Slavin MJ, Brodaty H, Crawford J, Xia A, Sachdev P: Discrete neuroanatomical networks are associated with specific cognitive abilities in old age. J Neurosci 2011;31:1204-1212.
7.
Geerligs L, Maurits NM, Renken RJ, Lorist MM: Reduced specificity of functional connectivity in the aging brain during task performance. Hum Brain Mapp 2012, E-pub ahead of print.
8.
Salat DH: The declining infrastructure of the aging brain. Brain Connect 2011;1:279-293.
9.
Greicius MD, Kimmel DL: Neuroimaging insights into network-based neurodegeneration. Curr Opin Neurol 2012;25:727-734.
10.
Buldu JM, Bajo R, Maestu F, Castellanos N, Leyva I, Gil P, Sendina-Nadal I, Almendral JA, Nevado A, del-Pozo F, Boccaletti S: Reorganization of functional networks in mild cognitive impairment. PLoS One 2011;6:e19584.
11.
Johansen-Berg H, Behrens TEJ: Diffusion MRI: From Quantitative Measurement to in-vivo Neuroanatomy. London, Elsevier, 2009.
12.
Fox MD, Raichle ME: Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 2007;8:700-711.
13.
Freitas C, Farzan F, Pascual-Leone A: Assessing brain plasticity across the lifespan with transcranial magnetic stimulation: why, how, and what is the ultimate goal? Front Neurosci 2013;7:42.
14.
Ferreira LK, Busatto GF: Resting-state functional connectivity in normal brain aging. Neurosci Biobehav Rev 2013;37:384-400.
15.
Baltes PB, Lindenberger U: Emergence of a powerful connection between sensory and cognitive functions across the adult life span: a new window to the study of cognitive aging? Psychol Aging 1997;12:12-21.
16.
Hampson M, Driesen N, Roth JK, Gore JC, Constable RT: Functional connectivity between task-positive and task-negative brain areas and its relation to working memory performance. Magn Reson Imaging 2010;28:1051-1057.
17.
Fling BW, Peltier SJ, Bo J, Welsh RC, Seidler RD: Age differences in interhemispheric interactions: callosal structure, physiological function, and behavior. Front Neurosci 2011;5:38.
18.
Langan J, Peltier SJ, Bo J, Fling BW, Welsh RC, Seidler RD: Functional implications of age differences in motor system connectivity. Front Syst Neurosci 2010;4:17.
19.
Antonenko D, Meinzer M, Lindenberg R, Witte AV, Floel A: Grammar learning in older adults is linked to white matter microstructure and functional connectivity. Neuroimage 2012;62:1667-1674.
20.
Antonenko D, Brauer J, Meinzer M, Fengler A, Kerti L, Friederici AD, Flöel A: Functional and structural syntax networks in aging. Neuroimage 2013;83C:513-523.
21.
Salami A, Eriksson J, Nyberg L: Opposing effects of aging on large-scale brain systems for memory encoding and cognitive control. J Neurosci 2012;32:10749-10757.
22.
Spreng RN, Schacter DL: Default network modulation and large-scale network interactivity in healthy young and old adults. Cereb Cortex 2012;22:2610-2621.
23.
Davis SW, Kragel JE, Madden DJ, Cabeza R: The architecture of cross-hemispheric communication in the aging brain: linking behavior to functional and structural connectivity. Cereb Cortex 2012;22:232-242.
24.
Chen NK, Chou YH, Song AW, Madden DJ: Measurement of spontaneous signal fluctuations in fMRI: adult age differences in intrinsic functional connectivity. Brain Struct Funct 2009;213:571-585.
25.
Lövdén M, Schmiedek F, Kennedy KM, Rodrigue KM, Lindenberger U, Raz N: Does variability in cognitive performance correlate with frontal brain volume? Neuroimage 2013;64:209-215.
26.
Madden DJ, Whiting WL, Huettel SA, White LE, MacFall JR, Provenzale JM: Diffusion tensor imaging of adult age differences in cerebral white matter: relation to response time. Neuroimage 2004;21:1174-1181.
27.
Friederici AD: The brain basis of language processing: from structure to function. Physiol Rev 2011;91:1357-1392.
28.
Turi Z, Paulus W, Antal A: Functional neuroimaging and transcranial electrical stimulation. Clin EEG Neurosci 2012;43:200-208.
29.
Meinzer M, Antonenko D, Lindenberg R, Hetzer S, Ulm L, Avirame K, Flaisch T, Flöel A: Electrical brain stimulation improves cognitive performance by modulating functional connectivity and task-specific activation. J Neurosci 2012;32:1859-1866.
30.
Meinzer M, Lindenberg R, Antonenko D, Flaisch T, Flöel A: Anodal transcranial direct current stimulation temporarily reverses age-associated cognitive decline and functional brain activity changes. J Neurosci 2013;33:12470-12478.
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