What is it about?
This study examines whether a single infusion of low-dose ketamine is associated with changes in thalamocortical functional connectivity (resting-state connectivity between the thalamus and cortical regions) in patients with treatment-resistant depression (TRD), including a subgroup with strong suicidal ideation. Using resting-state fMRI collected before infusion and again at day 3, the authors compared connectivity changes between ketamine and control conditions across two randomized, double-blind clinical trial samples.
Why is it important?
Treatment-resistant depression has been linked to disrupted brain network connectivity, and thalamocortical circuits are implicated in cognitive and emotional control. If ketamine is associated with measurable connectivity changes shortly after treatment, these patterns could help refine mechanistic models of ketamine’s rapid effects and inform future research on neuroimaging markers—while recognizing that connectivity shifts do not necessarily translate into symptom change.
Main findings
- Ketamine was associated with increases in specific thalamus–prefrontal connectivity patterns (e.g., increased connectivity with right middle frontal cortex in one trial; increased connectivity with anterior paracingulate cortex in the other).
- Ketamine was also associated with decreases in connectivity between the thalamus and regions linked to the default mode network (e.g., frontal pole/paracingulate targets), depending on the trial.
- Control infusions showed different (and in some instances opposite-direction) connectivity changes relative to ketamine in key thalamocortical connections.
- Associations between connectivity changes and changes in depressive or suicidal symptom measures did not remain statistically significant after multiple-comparison correction.
- Overall, the study identifies ketamine-related connectivity alterations, but does not establish a robust connectivity–symptom linkage within these samples.
What do the authors argue?
The authors argue that a single infusion of ketamine may alter thalamocortical functional connectivity in TRD, including circuits involving prefrontal and default mode network regions. However, because correlations between connectivity changes and clinical symptom improvements did not survive correction, they emphasize that whether these connectivity alterations are meaningfully tied to ketamine’s antidepressant and antisuicidal effects requires further investigation, ideally with larger samples and more consistent control conditions.
Team Member Spotlight
You can find the paper here.