Characterizing the primary olfactory subregions of the human amygdala

Several subregions of the human amygdala receive direct projections from the olfactory bulb, yet the functional and anatomical properties of these olfactory projections are not well understood. Rodent studies have begun to shed light on the functions of some of these olfactory amygdala subregions in mediating olfactory-guided social and approach/avoid behaviors. However, there are significant differences in the projections from the olfactory bulb to the amygdala between species. For example, in rodents, the medial amygdala receives highly dense fibers from the accessory olfactory bulb. In stark contrast, humans lack an accessory olfactory system entirely. There are also other apparent differences in the specific amygdalar targets of main olfactory bulb projections between species, although these targets have not been well-characterized in humans, further highlighting the need for human studies in this area. The goal of this proposal is to characterize the anatomical and functional properties of the olfactory projections into the human amygdala. We will take a multifaceted approach, combining functional neuroimaging, electrophysiology and stimulation, which will strengthen the reproducibility and rigor of our findings. The goal of Aim 1 is to anatomically and functionally localize the primary olfactory cortical regions of the human amygdala. At the structural level, we will use a novel new multi-shot diffusion-weighted imaging sequence to localize olfactory projections into amygdala subregions. At the functional level, we will use resting fMRI combined with k-means clustering algorithms to parcellate amygdalar subregions based on distinct whole-brain functional connectivity profiles, and event-related fMRI to functionally localize odor-responsive subregions of the amygdala. The goal of Aim 2 is to shed light on the roles of distinct amygdala subregions in olfactory perception. We will use event-related fMRI to acquire high-resolution multivariate signals from the amygdala during olfactory perceptual tasks. The goal of Aim 3 is to assess the necessity of the amygdala subregions in olfactory perception. We will use intracranial EEG techniques to measure different olfactory perceptual decisions during clinician-delivered, clinically prescribed, disruptive electrical stimulation directly into the human amygdala. The proposed studies will provide a detailed characterization of the functional and anatomical properties of an under-studied group of amygdala subregions, including the medial nucleus of the amygdala, the cortical amygdala and the periamygdaloid cortex. Recent studies suggest these anterior and medial amygdala areas may play a role in sudden unexpected death in epilepsy (SUDEP), which is the leading cause of death in patients with temporal lobe epilepsy and has no known cause or treatment. Furthering our understanding of the functional and structural properties of these brain regions has strong clinical importance for these patients.