Connectivity analysis with structural equation modelling: an example of the effects of voxel selection.

Structural equation modelling (SEM) of neuroimaging data is commonly applied to a network of distributed brain regions. We applied SEM to an fMRI dataset to identify condition-specific effects in a simple experiment composed of visual stimulation and baseline conditions. The visual network was composed of three well-defined anatomical regions (V1, V2, and V5) and three path connections (V1 --> V2, V1 --> V5, and V2 --> V5). This network was used to test four hypotheses: (1) whether the condition-specific effects for all three connections vary according to the data selected for modelling; (2) whether the "summary" measures that are often used are indeed appropriate; (3) whether measures taken from the voxel timecourse can reliably predict the condition-specific effects for each one of the three path connections, and (4) whether all voxels within an anatomical region yield equivalent SEM outcomes. There was some variability in the significance of the condition-specific effects across randomly selected voxels within regions. However, the SEM outcome from the "summary" measures was comparable to the most frequent pattern of condition-specific effects. Magnitude, delay, spread, and goodness-of-fit measures taken from a gamma fit to the voxel time courses predicted reliably the significance of the SEM condition-specific effects for each connection. This result enabled us to identify spatially coherent regions at the boundaries of V2 that displayed different condition-specific effects from those seen in the majority of the voxels. Although the generality of these results awaits further investigation, this example highlights a number of important issues for SEM. We have provided further evidence that the SEM outcome does vary somewhat according to the voxels selected and that, although the use of summary measures can give a generalised view of the connectivity pattern, they could fail to capture functional differences within specialised areas.