Hi Nicola,
Interestingly you can actually combine -seed_gmwmi and -seed_image in a single tckgen call. The relative number of seeds drawn in each would be dependent on the relative volumes of the two seed images, which may or may not be “ideal” in any sense. Also, using the default output of 5tt2gmwmi as the input to -seed_gmwmi will actually seed streamlines “at” the sub-cortical grey matter structures, just at their interfaces with white matter rather than inside of them. But for whole-brain tractography intended for SIFT2 I don’t know that there is any situation in which I would advise not using dynamic seeding and instead using a less data-driven alternative.
The condition for SIFT2 to be applicable in this context is that the input tractogram needs to be whole-brain. If the particular type of seeding used tends to over-reconstruct or under-reconstruct certain pathways, that’s fine, that’s exactly what SIFT2 aims to address. But where it starts to break down is if pathways are wholly absent from the tractogram, whether due to the inability to reconstruct such or erroneous removal of such streamlines by the user prior to SIFT2.
As far as your final point, I’m not sure whether or not my interpretation is correct, so I’ll spell that out in addition to my response. What it sounds like is that, instead of a streamline traversing from cortical region A to cortical region B, the streamline instead (perhaps erroneously) intersects sub-cortical region C and thus terminates, resulting in a connection from A to C. I’ve had this problem myself reconstructing the CST when using ACT: over-estimation of the spatial extent of sub-cortical grey matter structures, combined with the ‘wiggliness’ of iFOD2 with the default power parameter, makes it rare for streamlines to traverse the entire internal capsule unimpeded. It’s true that in some instances this may be a combined false positive & false negative, especially if talking about tensor-based tractography. An alternative consideration is that it’s entirely possible that when performing whole-brain tractography, another streamline will be produced from cortical region B to the same part of sub-cortical region C, such that the connection from A to B is sort of present, it’s just via a second-order connection through C. There’s scope for alteration of analyses to take such data into account in a sensible way, but it might be too tangential given your actual question.
Cheers
Rob