help > Mixed-effects design with within-patient cross-over in CONN
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Sep 15, 2025  12:09 PM | Vanessa Vallesi
Mixed-effects design with within-patient cross-over in CONN

Dear CONN community,


I am working with a within-patient cross-over design and would appreciate your thoughts on my strategy to analyse functional connectivity in CONN.


Design
Each participant underwent 4 resting-state fMRI sessions:




  1. Baseline




  2. Treatment or placebo phase




  3. Baseline (after wash-out)




  4. The alternate phase (placebo or treatment)




The order of treatment/placebo was counterbalanced.


Goal
Previous work shows a robust treatment effect on functional connectivity (FC) in two predefined networks (seed-based).
I would like to test:




  • within-subject effects of treatment vs. placebo




  • patient-level effects (between-subject variability)





Because CONN currently does not implement mixed-effects linear models across multiple sessions, my idea was to:




  • Compute FC in the predefined networks and set up a contrast that averages the effect across all four sessions (e.g. baseline, treatment/placebo, baseline, treatment/placebo weighted 1/4 each).




  • Extract the resulting subject-level FC values.




  • Run a mixed-effects model in R, using participant ID and timepoint as random factors and treatment as the fixed effect.




Would you consider this a valid workflow, or would you recommend a different modelling strategy within CONN (e.g. a different second-level design or custom contrasts) before exporting the data?


Many thanks in advance.


Best regards,
Vanessa