Abstract
Subanesthetic ketamine is found to induce fast-acting and pronounced antidepressant effects, even in treatment resistant depression (TRD). However, it remains unclear how ketamine modulates neural function at the brain systems-level to regulate emotion and behavior. Here, we examined treatment-related changes in the inhibitory control network after single and repeated ketamine therapy in TRD. Forty-seven TRD patients (mean age = 38, 19 women) and 32 healthy controls (mean age = 35, 18 women) performed a functional magnetic resonance imaging (fMRI) response inhibition task at baseline, and 37 patients completed the fMRI task and symptom scales again 24 h after receiving both one and four 0.5 mg/kg intravenous ketamine infusions. Analyses of fMRI data addressed effects of diagnosis, time, and differences between treatment remitters and non-remitters. Significant decreases in brain activation were observed in the inhibitory control network, including in prefrontal and parietal regions, and visual cortex following serial ketamine treatment, p < 0.05 corrected. Remitters were distinguished from non-remitters by having lower functional activation in the supplementary motor area (SMA) prior to treatment, which normalized towards controls following serial ketamine treatment. Results suggest that ketamine treatment leads to neurofunctional plasticity in executive control networks including the SMA during a response-inhibitory task. SMA changes relate to reductions in depressive symptoms, suggesting modulation of this network play an important role in therapeutic response. In addition, early changes in the SMA network during response inhibition appear predictive of overall treatment outcome, and may serve as a biomarker of treatment response.
Highlights
Major depression is the world’s leading cause of years lost to disability[1]
Our primary results revealed that serial ketamine infusion induces a robust decrease in functional magnetic resonance imaging (fMRI) activity in brain regions associated with response inhibition[21,33], including dorsolateral prefrontal cortex (DLPFC) along with areas in the superior and inferior parietal lobules
This significant decrease in fMRI activity was observed across various large-scale networks[51] such as the default mode network (DMN), fronto-parietal network (FPN), dorsal-attention network (DAN), and the salience network (SAN) in the right hemisphere following ketamine treatment (Supplementary Fig. S1)
Summary
Major depression is the world’s leading cause of years lost to disability[1]. many patients benefit from first-line monoaminergic antidepressants, therapeutic response can take weeks or longer[2] and a third of patients, defined as having treatment resistant depression (TRD), will remain refractory to two or more treatment trials[3,4]. To determine whether ketamine modulates dysfunctional inhibitory mechanisms reported in major depression[17,18], the present study used an event-related design during a response inhibition Go/NoGo functional magnetic resonance imaging (fMRI) task in TRD patients followed prospectively through a series of four subanesthetic intravenous (IV) ketamine treatments. Mean ROI contrast values were used to establish whether neural response after single infusion (TP1–TP2) relates to percent change in HDRS scores after serial ketamine (TP1–TP3).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
