Locally Estimated Hemodynamic Response Function and Activation Detection Sensitivity in Heroin-Cue Reactivity Study

Introduction: A fixed hemodynamic response function (HRF) is commonly used for functional magnetic resonance imaging (fMRI) analysis. However, HRF may vary from region to region and subject to subject. We investigated the effect of locally estimated HRF (in functionally homogenous parcels) on activation detection sensitivity in a heroin cue reactivity study. Methods: We proposed a novel exploratory method for brain parcellation based on a probabilistic model to segregate the brain into spatially connected and functionally homogeneous components. Then, we estimated HRF and detected activated regions in response to an experimental task in each parcel using a joint detection estimation (JDE) method. We compared the proposed JDE method with the general linear model (GLM) that uses a fixed HRF and is implemented in FEAT (as a part of FMRIB Software Library, version 4.1). Results: 1) Regions detected by JDE are larger than those detected by fixed HRF, 2) In group analysis, JDE found areas of activation not detected by fixed HRF. It detected drug craving a priori “regions-of-interest” in the limbic lobe (anterior cingulate cortex [ACC], posterior cingulate cortex [PCC] and cingulate gyrus), basal ganglia, especially striatum (putamen and head of caudate), and cerebellum in addition to the areas detected by the fixed HRF method, 3) JDE obtained higher Z-values of local maxima compared to those obtained by fixed HRF. Conclusion: In our study of heroin cue reactivity, our proposed method (that estimates HRF locally) outperformed the conventional GLM that uses a fixed HRF.