Ketamine-related neural changes in treatment-resistant depression: A multimodal synthesis of fMRI and PET studies

Ketamine produces rapid antidepressant effects in a subset of patients with treatment-resistant depression, yet neuroimaging findings have been difficult to integrate because studies differ in imaging modality, analytic approach, task context, and post-infusion timing. To address this, we conducted a multimodal synthesis of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) studies of ketamine in adults with treatment-resistant depression, integrating region-level inspection and functional network mapping to evaluate patterns across heterogeneous designs. The findings suggest that ketamine-related effects were frequently reported in subcortical regions, alongside more distributed and context-dependent effects across cortical systems, including prefrontal and anterior cingulate regions. Network-level summaries further suggested involvement of default-mode, ventral attention, and visual systems. Given variability in imaging modality, task state, and scan timing, these results should be interpreted as hypothesis-generating and motivate future harmonized multimodal studies designed to directly link circuit-level changes to molecular mechanisms and clinical response.