Longitudinal degeneration of microstructural and structural connectivity patterns following stroke

Stroke leads to neurological impairment through local and widespread brain damage. Whether distal and local diffusivity changes follow similar reorganization and behavior correlation trajectories is unclear. We examined acute and chronic brain diffusivity changes in stroke patients using both connectivity and microstructural parameters, hypothesizing similar trajectories linked with behavioral scores. This perspective study assessed first-time stroke patients at two weeks and three months using behavioral tests and diffusion MRI. We applied latent factorial analysis to behavioral and microstructural data from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) outcomes. Structural connectivity gradients were computed from whole brain tractography. Statistical analyses included cross-sectional analyses, longitudinal linear mixed models, and the assessment of the relationship between microstructure and contralateral dysconnectivity. Finally, we explored the linear relationships between diffusivity parameters and behavior. Seventy-nine patients (60+12 years) were enrolled, with 32 completing follow-up (3 months). A healthy group of n=33 (58+11 years) was included. Factorial analysis identified five latent factors explaining about 50% of behavioural variances. We described three main DTI-NODDI microstructural maps and three main structural gradients, capturing around 50% of variance each. The analysis revealed acute alterations of microstructural and connectivity patterns. Longitudinally, significant degeneration in structural connectivity was observed, echoed in microstructural parameters. Behaviourally, global structural connectivity alterations were associated with acute cognitive deficits, though this link weakened at chronic follow-up. On the contrary, local disconnectivity patterns were linked mainly with motor deficits. Finally, we reported a significant association between global connectivity alterations and microstructural changes in tracts locally disconnected. Stroke significantly alters diffusivity patterns beyond the lesion, with no recovery over time. While acute-stage effects relate to behavior, long-term connectivity changes seem mostly uncoupled, suggesting they do not correlate with stroke recovery.