Measurement of spontaneous signal fluctuations in fMRI: adult age differences in intrinsic functional connectivity

Abstract

Functional connectivity (FC) reflects the coherence of spontaneous, low-frequency fluctuations in functional magnetic resonance imaging (fMRI) data. We report a behavior-based connectivity analysis method, in which whole-brain data are used to identify behaviorally relevant, intrinsic FC networks. Nineteen younger adults (20-28 years) and 19 healthy, older adults (63-78 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 age-related change in the correlation with perceptual-motor speed (choice reaction time; RT). No relation between FC and RT was evident for younger adults, whereas older adults exhibited a significant age-related slowing of perceptual-motor 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. The developed FC analysis illustrates the value of identifying connectivity by combining structural, functional, and behavioral data.

Figures

Fig 1

Comparison of different approaches for calculating the relation between intrinsic functional connectivity (FC) and behavioral performance: seed-based region of interest (ROI; Panel A), independent components analysis (ICA; Panel B), and the BBCA method (Panel C). In comparison to conventional approaches (A and B), the BBCA method (C) integrates behavioral data at an early stage of processing, and evaluates the behavioral relevance of all intrinsic connectivity networks without a priori assumptions regarding the relevant regions. An FC matrix of all possible pairwise comparisons is first calculated for each subject (Panel C.1). By correlating the FC measures with the behavioral data across subjects (Panel C.2), the behaviorally-relevant FC can be identified with a pre-defined threshold (Panel C.3)

Fig 2

Events occurring within each imaging run. Participants first performed a word encoding task (pleasant/unpleasant judgment of individual words) during diffusion tensor imaging (DTI). During a following functional magnetic resonance imaging (fMRI) run, participants performed a choice reaction time (RT) task (left/right key press), followed by an off-task period, and a memory retrieval task. The nature of the retrieval task, episodic versus semantic, alternated across runs. The episodic task required a yes/no judgment as to whether the current word was presented during encoding. The semantic task required a living/nonliving judgment regarding the referent of the word, without reference to the word's presence in the encoding list

Fig 3

Examples of the regions of interest ROIs used in the analysis of the diffusion tensor imaging (DTI) data, modified from Bucur et al. (2008). Panel A = raw DTI image. Panel B = regions located on DTI images with maximum value for image intensity lowered. UNC = uncinate fasciculus; PCF = pericallosal frontal; GNU = genu of corpus callosum; SPN = splenium of corpus callosum; CIN = cingulum bundle; ASL = anterior portion of the superior longitudinal fasciculus; PSL = posterior portion of the superior longitudinal fasciculus. The z values are mm superior/inferior to the anterior commissure

Fig 4

Regional connectivity matrix for the 116 anatomical regions in the Tzourio-Mazoyer (2002) template. Within each cell of the matrix, the grayscale value represents the signal coherence level (Zr) between two regions (Panel A). For example, A 2 × 2 orange cluster (consisting of four neighboring matrix cells) represents the signal coherence levels between left/right medial prefrontal cortex (orbital; illustrated by red arrow) and left/right posterior cingulate (illustrated by yellow arrow). Panel B illustrates the location of medial prefrontal cortex (orbital) and posterior cingulate in a sagittal view

Fig 5

In the regional connectivity matrix for older adults, 19 pairs of regions (indicated by red lines) were correlated significantly (p < 0.005) with perceptual-motor speed (choice reaction time; RT). The inferior frontal gyri were involved in 13 of these networks, indicating a role of the inferior frontal cortex in behaviorally-relevant functional connectivity (FC) for older adults. No regional connections were significant for younger adults at this threshold. For description of abbreviations, see Table 1 note

Fig 6

Relation between choice reaction time (RT) and functional connectivity (in networks connected with inferior frontal gyri), for younger adults (Panel A) and older adults (Panel B)

Fig 7

Relation between white matter integrity (fractional anisotropy) in the genu of the corpus callosum and functional connectivity (in networks connected with inferior frontal gyri), for older adults