Davide Imperati

The network architecture of functional connectivity within the human brain connectome is poorly understood at the voxel level. Here, using resting state functional magnetic resonance imaging data from 1003 healthy adults, we investigate a broad array of network centrality measures to provide novel insights into connectivity within the whole-brain functional network (i.e., the functional connectome). We first assemble and visualize the voxel-wise (4 mm) functional connectome as a functional network. We then demonstrate that each centrality measure captures different aspects of connectivity, highlighting the importance of considering both global and local connectivity properties of the functional connectome. Beyond "detecting functional hubs," we treat centrality as measures of functional connectivity within the brain connectome and demonstrate their reliability and phenotypic correlates (i.e., age and sex). Specifically, our analyses reveal age-related decreases in degree centrality, but not eigenvector centrality, within precuneus and posterior cingulate regions. This implies that while local or (direct) connectivity decreases with age, connections with hub-like regions within the brain remain stable with age at a global level. In sum, these findings demonstrate the nonredundancy of various centrality measures and raise questions regarding their underlying physiological mechanisms that may be relevant to the study of neurodegenerative and psychiatric disorders.

Even in the simplest laboratory tasks older adults generally take more time to respond than young adults. One of the reasons for this age-related slowing is that older adults are reluctant to commit errors, a cautious attitude that prompts them to accumulate more information before making a decision (Rabbitt, 1979). This suggests that age-related slowing may be partly due to unwillingness on behalf of elderly participants to adopt a fast-but-careless setting when asked. We investigate the neuroanatomical and neurocognitive basis of age-related slowing in a perceptual decision-making task where cues instructed young and old participants to respond either quickly or accurately. Mathematical modeling of the behavioral data confirmed that cueing for speed encouraged participants to set low response thresholds, but this was more evident in younger than older participants. Diffusion weighted structural images suggest that the more cautious threshold settings of older participants may be due to a reduction of white matter integrity in corticostriatal tracts that connect the pre-SMA to the striatum. These results are consistent with the striatal account of the speed-accuracy tradeoff according to which an increased emphasis on response speed increases the cortical input to the striatum, resulting in global disinhibition of the cortex. Our findings suggest that the unwillingness of older adults to adopt fast speed-accuracy tradeoff settings may not just reflect a strategic choice that is entirely under voluntary control, but that it may also reflect structural limitations: age-related decrements in brain connectivity.

Animal models of stroke demonstrated that white matter ischemia may cause both axonal damage and myelin degradation distant from the core lesion, thereby impacting on behavior and functional outcome after stroke. We here used parameters derived from diffusion magnetic resonance imaging (MRI) to investigate the effect of focal white matter ischemia on functional reorganization within the motor system. Patients (n = 18) suffering from hand motor deficits in the subacute or chronic stage after subcortical stroke and healthy controls (n = 12) were scanned with both diffusion MRI and functional MRI while performing a motor task with the left or right hand. A laterality index was employed on activated voxels to assess functional reorganization across hemispheres. Regression analyses revealed that diffusion MRI parameters of both the ipsilesional corticospinal tract (CST) and corpus callosum (CC) predicted increased activation of the unaffected hemisphere during movements of the stroke-affected hand. Changes in diffusion MRI parameters possibly reflecting axonal damage and/or destruction of myelin sheath correlated with a stronger bilateral recruitment of motor areas and poorer motor performance. Probabilistic fiber tracking analyses revealed that the region in the CC correlating with the fMRI laterality index and motor deficits connected to sensorimotor cortex, supplementary motor area, ventral premotor cortex, superior parietal lobule, and temporoparietal junction. The results suggest that degeneration of transcallosal fibers connecting higher order sensorimotor regions constitute a relevant factor influencing cortical reorganization and motor outcome after subcortical stroke.