Modulation of functional network co-activation pattern dynamics following ketamine treatment in major depression.
Brandon Taraku, Jason S Nomi, Artemis Zavaliangos-Petropulu, Noor B. Al-Sharif, Paloma Pfeiffer, Viviane Norris, Shantanu Joshi, Randall Espinoza, Lucina Q. Uddin, Katherine L Narr
Imaging neuroscience (Cambridge, Mass.) 2025 DOI: 10.1162/imag.a.936 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 58 |
| Population | Adults with treatment-resistant depression |
| Intervention | Ketamine infusions |
| Dose | 0.5 mg/kg |
| Duration | 4 infusions over 2 weeks; assessments at baseline and 24 hours after the last infusion |
| Topics | Depression Ketamine Esketamine |
| Keywords | Central executive network Co-activation patterns Dynamic functional connectivity Rumination Salience network |
| Key findings | Ketamine treatment in treatment-resistant depression alters dynamic functional connectivity, increasing time spent in central executive network states and salience-to-central executive transitions, while decreasing visual network states and salience-to-visual transitions, with changes in salience network dynamics linked to reduced rumination. |
Abstract
Ketamine produces fast-acting antidepressant effects in treatment-resistant depression (TRD). Prior studies have shown altered functional dynamics between brain networks in major depression. We thus sought to determine whether functional brain network dynamics are modulated by ketamine therapy in TRD. Participants with TRD (n = 58, mean age = 40.7 years, female = 48.3%) completed resting-state fMRI scans and clinical assessments (mood and rumination) at baseline and 24 h after receiving 4 ketamine infusions (0.5 mg/kg) over 2 weeks. Healthy controls (HC) (n = 56, mean age = 32.8 years, female = 57.1%) received the same assessments at baseline and after 2 weeks in a subsample without treatment. A co-activation pattern (CAP) analysis identified recurring patterns of brain activity across all subjects using k-means clustering. Statistical analyses compared CAP metrics including the fraction of time (FT) spent in a brain state, and the transition probability (TP) from one state to another over time and associations with clinical improvement. Follow-up analyses compared HC and TRD at baseline. Six brain state clusters were identified, including patterns resembling the salience (SN), central executive (CEN), visual (VN), default mode (DMN), and somatomotor (SMN) networks. Following ketamine treatment, TRD patients showed decreased FT for the VN (p = 7.4E-04) and increased FT for the CEN state (p = 1.9E-03). For TP metrics, SN-CEN increased (p = 5.8E-04) and SN-VN decreased (p = 3.6E-03). Decreased FT for the SN associated with improved rumination (p = 1.9E-03). At baseline, lower FT for CEN (p = 5.70E-04) and TP for SN-CEN (p = 0.016) and higher TP for SN-VN (p = 2.60E-03) distinguished TRD from HCs. CAP metrics remained stable over time in a subsample of HCs (n = 18). These findings suggest ketamine modulates brain network dynamics between SN, CEN, and VN in TRD, which may normalize dynamic patterns seen in TRD at baseline toward patterns seen in controls. Changes in SN state dynamics may correspond to improvements in ruminative symptoms following ketamine therapy.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
| Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... | 2017 | Observational cohort | n = 59 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |