Questions about connectometry in brain-injured patients

[Yusheng Wang]

Hi Frank,

I hope you are doing well! I’m currently working with a cohort of brain-injured patients (mostly with stroke or focal lesions), and I’m considering using connectometry to explore the relationship between white matter integrity and behavioral performance.

I had two conceptual and practical questions, especially in the context of lesion data:

1. On the conceptual level:
If I understand correctly, connectometry performs a voxel-wise correlation between a diffusion metric (e.g., QA, FA) and a behavioral score, and then reconstructs tracts passing through the significant voxels. My concern is that this approach seems analogous to TBSS, but unconstrained by predefined tracts.

However, if the hypothesis is about disconnection between specific brain regions, wouldn't any lesion along the connecting tract lead to similar behavioral consequences? That is, the functional impact is not necessarily localized to a specific voxel but can occur anywhere along the pathway. In that case, voxel-wise association might highlight "confluence points" where multiple tracts meet, but miss diffuse or distributed disconnections that matter just as much.

Would this make connectometry less sensitive to detecting distributed disconnection effects in such scenarios? Why would you expect the behavioral relationship with sort of disconnections to be carried in particular voxels, rather than loss of particular connections?

2. On the tractography step:
After identifying significant voxels, I understand that connectometry reconstructs tracks passing through those regions. My question is: in lesion patients, these regions may be structurally damaged and may no longer support valid tractography.
In such cases, does connectometry perform tractography using each patient's own data (which may be impaired), or does it reference normative tractography (e.g., from control subjects or a template) to reconstruct the tracks through those significant voxels?

I’d really appreciate any clarification you could provide, especially regarding the best practices when applying connectometry in clinical populations with structural brain damage. If you have any suggested references, I would greatly appreciate it!

Best,
Yusheng