Abstract
Task-state functional connections – such as those measured using functional MRI (fMRI) – are thought to coordinate distributed cognitive processes throughout the brain. Utilizing a neural mass computational model we found that the conversion of neural signals into fMRI hemodynamic responses substantially and inappropriately inflates task-state functional connectivity (FC) estimates (temporal correlations). Such activation-induced inflation of task FC estimates was postulated previously, but this phenomenon has not been conclusively established either theoretically or empirically, leading many task FC studies to simply ignore the issue. We found that activation-based task FC inflation was primarily driven by task-evoked fMRI activations introducing a similar hemodynamic response shape to underlying neural time series. This demonstrates that isolating task-state network changes from task-evoked activations is essential for ensuring discovery of unique functional network effects, independent of mechanistically-distinct activation effects. Standard approaches for fitting and removing task-evoked activations were unable to correct these inflated correlations. In contrast, methods that flexibly fit hemodynamic response shapes (especially finite impulse response-based regression) effectively corrected the inflated correlations. Results with empirical fMRI data confirmed the model’s predictions, revealing activation-induced task FC inflation for both Pearson correlation and psychophysiological interaction approaches. These results demonstrate that removal of task activations using an approach that flexibly models hemodynamic response shape is an essential preprocessing step for valid estimation of task-state FC with fMRI.
Highlights
Computational model shows task inflation of functional connectivity estimates
Hemodynamic response shape causes task activations to further inflate estimates
Standard approach to remove task activations leaves many false positives
Methods that flexibly fit hemodynamic response shape effectively correct inflation
Correction of functional connectivity inflation verified with empirical fMRI data