Normal aging in mice is associated with a global reduction in cortical spectral power and network-specific declines in functional connectivity
Asher J. Albertson,
Eric C. Landsness,
Michelle J. Tang,
Ping Yan,
Hanyang Miao,
Zachary P. Rosenthal,
Byungchan Kim,
Joseph C. Culver,
Adam Q Bauer,
Jin-Moo Lee
Affiliations
Asher J. Albertson
Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA
Eric C. Landsness
Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA
Michelle J. Tang
Duke University School of Medicine, DUMC 3878, Durham, NC 27710, USA
Ping Yan
Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA
Hanyang Miao
Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA
Zachary P. Rosenthal
Medical Scientist Training Program, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA
Byungchan Kim
Boston University School of Medicine, 72 East Concord St., Boston, MA 02118, USA
Joseph C. Culver
Department of Radiology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA; Department of Biomedical Engineering, Washington University, 1 Brookings Drive, St. Louis, MO, 63130, USA; Department of Physics, Washington University, 1 Brookings Drive, St. Louis, MO 63130, USA; Department of Electrical and Systems Engineering, Washington University, 1 Brookings Drive, St. Louis, MO 63130, USA
Adam Q Bauer
Department of Radiology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA; Department of Biomedical Engineering, Washington University, 1 Brookings Drive, St. Louis, MO, 63130, USA; Corresponding authors.
Jin-Moo Lee
Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA; Department of Radiology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA; Department of Biomedical Engineering, Washington University, 1 Brookings Drive, St. Louis, MO, 63130, USA; Corresponding authors.
Normal aging is associated with a variety of neurologic changes including declines in cognition, memory, and motor activity. These declines correlate with neuronal changes in synaptic structure and function. Degradation of brain network activity and connectivity represents a likely mediator of age-related functional deterioration resulting from these neuronal changes. Human studies have demonstrated both general decreases in spontaneous cortical activity and disruption of cortical networks with aging. Current techniques used to study cerebral network activity are hampered either by limited spatial resolution (e.g. electroencephalography, EEG) or limited temporal resolution (e.g., functional magnetic resonance imaging, fMRI). Here we utilize mesoscale imaging of neuronal activity in Thy1-GCaMP6f mice to characterize neuronal network changes in aging with high spatial resolution across a wide frequency range. We show that while evoked activity is unchanged with aging, spontaneous neuronal activity decreases across a wide frequency range (0.01–4 Hz) involving all regions of the cortex. In contrast to this global reduction in cortical power, we found that aging is associated with functional connectivity (FC) deterioration of select networks including somatomotor, cingulate, and retrosplenial nodes. These changes are corroborated by reductions in homotopic FC and node degree within somatomotor and visual cortices. Finally, we found that whole-cortex delta power and delta band node degree correlate with exploratory activity in young but not aged animals. Together these data suggest that aging is associated with global declines in spontaneous cortical activity and focal deterioration of network connectivity, and that these reductions may be associated with age-related behavioral declines.
