Effect of ketamine intervention on hemodynamic responses in patients with treatment-resistant depression

Emerging evidence shows that ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, can produce rapid anti-suicidal effects in treatment-resistant depression, yet its underlying neuropharmacological mechanisms remain elusive. The present study aimed at investigating the therapeutic effect of ketamine infusion on suicidal ideation by examining hemodynamic response changes in resting-state fMRI (rsfMRI) data. We analyzed data from clinical trials involving 45 patients with treatment-resistant depression, including either ketamine (N = 21) or midazolam (N = 24). T1-weighted images and rsfMRI data were collected before and three days after treatment. Three parameters, including response height (RH), time-to-peak (TTP), and full-width at half-maximum (FWHM), were extracted. Results showed that ketamine significantly altered TTP and FWHM in the bilateral olfactory cortex and right inferior parietal gyrus. Changes in TTP and FWHM within the thalamus and superior frontal gyrus were associated with improvements in suicidal ideation. Additionally, ketamine responders exhibited reduced TTP in the left precuneus. These findings suggest that ketamine induces region-specific HRF modulations in brain regions implicated in sensory-cognitive integration, mood regulation, and cognitive control. This supports a broader model in which ketamine's neuropharmacological effects may be understood through the lens of neurovascular coupling dynamics.