Effects of olfactory training on resting-state effective connectivity in patients with posttraumatic olfactory dysfunction

The present study investigated if and how the smell training scheme affects resting‑state effective connectivity. We focused on connectivity among brain regions that participate in olfactory‑related processes, including the piriform cortex, amygdala, orbitofrontal cortex (OFC), insula, and cingulate cortex. Sixteen patients with posttraumatic olfactory dysfunctions between the ages of 18 and 36 years participated in this study. Olfactory performance of subjects was evaluated using the Sniffin' Sticks test kit and then, resting‑state functional magnetic resonance imaging (fMRI) was performed. Of the 16 participants, 8 underwent olfactory training for 16 weeks and the remaining 8 did not receive the treatment (the control group). After 16 weeks, participants in both groups underwent the same procedure (smell testing and the MRI examination). Olfactory performance scores were compared between groups using an independent samples t‑test. Spectral dynamic causal modeling was applied to resting‑state fMRI data to identify alterations in effective connectivity due to the smell training. We found that patients in the treatment group improved in the odor discrimination task and overall olfactory function as compared to the control group. Compared to the control group, patients in the treatment group had increased self‑inhibitory connectivity of the OFC and increased excitatory connectivity from the cingulate cortex to the insula. Moreover, the excitatory connectivity from the OFC to the cingulate cortex was found to be weaker following the olfactory training scheme. This study shows that a smell training scheme can cause changes in resting‑state effective connectivity parameters that can be attributed to improvements in the odor discrimination task.