Title: Measurement of Spontaneous Signal Fluctuations in fMRI: A New Method and Application to Aging Authors: Nankuei Chen, Yinghui Chou, David J. Madden Submitted to: Brain Structure and Function (2009) Abstract: Functional connectivity (FC) reflects the coherence of spontaneous, lowfrequency fluctuations in functional magnetic resonance imaging (fMRI) data. We report a new data analysis method, in which wholebrain data are used to define behaviorallyrelevant, intrinsic FC networks. Nineteen younger adults (2028 years) and 19 healthy, older adults (6378 years) were assessed with fMRI and diffusion tensor imaging (DTI). Results indicated that FC involving a distributed network of brain regions, particularly the inferior frontal gyri, exhibited agerelated change in the correlation with perceptualmotor speed (choice reaction time; RT). No relation between FC and RT was evident for younger adults, whereas older adults exhibited a significant agerelated slowing of perceptualmotor speed, which was mediated by decreasing FC. Older adults’ FC values were in turn associated positively with white matter integrity (from DTI) within the genu of the corpus callosum. This new method of FC analysis illustrates the value of identifying connectivity by combining structural, functional, and behavioral data.