Subregional amygdala functional connectivity at 3T: comparison of high-resolution 2D and 3D fMRI acquisitions

Background and Purpose: Amygdala dysfunction is implicated in major depressive disorder. Despite wide acknowledgement of its heterogeneity, the amygdala is predominantly considered as a single entity and functional connectivity investigations have reported findings using standard or low spatial resolution functional MRI data. This study compared the capabilities of two high spatial resolution acquisition strategies, the gold standard 2D and a novel 3D, in identifying amygdala functional connectivity to other brain regions at a subregional level. Methods: Resting state fMRI data were acquired at 3T in 10 healthy controls using both versions of a Gradient-Echo Echo Planar Imaging (GRE-EPI) sequence. Whole brain voxel-wise functional connectivity measures were calculated using the whole amygdala and six subregional seed regions-of-interest; left and right basolateral, centromedial and superficial. Results: The 3D data identified multiple stronger bilateral connections between both centromedial subregions, most notably to subcortical structures including brainstem and hippocampus, as well as intra-amygdala subregional connections. The 2D data displayed stronger connections to several cortical regions. Whole amygdala and subregional FC results differed. Conclusions: This study identified underutilized capability in current fMRI acquisition techniques at 3T. 2D GRE-EPI sequences optimized for high spatial resolution with voxel volumes of 15.6 mm³ capably demonstrate functional connectivity patterns of the amygdala at a subregional level, allowing interrogation of heterogeneous amygdala function at a more granular level. The novel 3D acquisition with voxel volumes of 8 mm³ showed promise in outperforming its 2D counterpart in identifying amygdala subregional connections to other subcortical structures that are traditionally difficult to image well.