Table 3.

Comparison of key models for PET quantification and fMRI analysis that capture time-dependent changes during a scan.

Functional MRI method	Description	Key assumptions	Features	Limitations
Functional MRI: block or event-related31,33	Task-based or repeated stimulus intervention assessed by a general linear model (GLM).	Shape of the hemodynamic response function due to neuronal activation.	Robust outcome measures together with appropriate statistics and with sufficient repetitions within an experiment.	Interventions that are long-lived may not be distinguishable from baseline. Physiological noise can be a barrier in certain cases.
Pharmacological MRI12	Functional MRI with a pharmaceutical as the intervention.	Timecourse of the pharmacological intervention may be data-driven or based on knowledge from PK/PD.	Evaluation of hemodynamic changes due to a pharmaceutical.	Effects of drugs that have many targets may be more complex to interpret with phMRI alone.
Functional connectivity139	Resting-state or task-activated functional connectivity between brain regions with synchronous temporal activity or fluctuations.	Brain regions that display synchronous activity are functionally connected.	Mainly a data-driven approach with several analysis technique choices.	No directionality.