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.