Figure 1.

Potential longitudinal connectivity changes in ALS. This figure shows four potential scenarios for longitudinal neurodegeneration in ALS and the hypothesized results of the two types of analyses. A: Progressive impairment within a subnetwork of initially impaired structural connections and regions will be detected by Analysis 2. Analysis 1 will not detect this type of progressive degeneration. B: If the degenerative changes over time show spatial spread within the brain, this will be detected by Analysis 1 as this will result in an expanding subnetwork of impaired connections. (A + B) The third scenario is a combination of both progressive impairment of initially impaired structural connections, as well as expansion of the impaired connectivity (i.e., scenario A and B combined). In this scenario, both analyses show positive results. C: The fourth scenario is longitudinal degeneration involving distant structural connections to the initially impaired subnetwork or multifocal degeneration. As the NBS analysis is designed to detect changes within a network, both Analysis 1 and 2 will show negative results when distant structural connections become impaired over time. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]