Abstracts

Rationale:
Bottom-of-sulcus dysplasia (BOSD) is an important cause of intractable epilepsy, characterised by a highly localised dysplastic lesion. Increasing evidence from other focal epilepsies suggests that focal lesions are associated with widespread disruption of large-scale brain networks; however, it remains unclear if BOSD is similarly characterised by network abnormalities. By applying a technique known as fixel-based analysis (where the term ‘fixel’ refers to a specific population of fibres within a single voxel), we can investigate changes to structural connectivity in specific fibre tracts. In this study, we investigate whether BOSD patients exhibit structural abnormality in their brain networks.
Method:
Whole-brain fixel-based analysis of diffusion MRI data was performed to identify specific white matter tracts that exhibit reductions in fibre density and cross-section (FDC) in BOSD patients (n = 21) when compared to healthy age- and sex-matched control participants (n = 42). Exploratory post-hoc analyses were performed on the affected tracts, by extracting mean FDC from BOSD patients, and investigating relationships with clinical disease features. The relationship between FDC with seizure frequency and disease duration were explored in the select tracts-of-interest.
Results:
BOSD patients exhibited widespread structural connectivity reductions to white matter fibre tracts, including the bilateral corticospinal, corticothalamic, and cerebellothalamic tracts, superior longitudinal fasciculi, the forceps major, and body of the corpus callosum (Figure 1). Fibre tract density and cross-sectional reductions were observed bilaterally, which persisted even after aligning the epileptic side in all cases. Tract FDC in the forceps major exhibited the strongest association with seizure frequency out of all tracts, while the strongest association between tract FDC and disease duration was observed in the corticospinal tracts (Figure 2).
Conclusion:
BOSD patients exhibit common disruption to specific white matter pathways which may reflect selective vulnerability of structural brain networks in BOSD. The results of our post-hoc analyses suggest that disruption to certain fibre tracts (in particular, the forceps major and corticospinal tracts) is likely related to seizure activity, while we speculate that disruption to other tracts may be developmental in origin or related to other causes.
Funding:
:We are grateful to the National Health and Medical Research Council (NHMRC) of Australia for their funding support. This project was supported by a NHMRC grant (Grant number: 1091593).