Modulation of functional network co-activation pattern dynamics following ketamine treatment in major depression.
Brandon Taraku, Jason S Nomi, Artemis Zavaliangos-Petropulu, Noor Al-Sharif, Paloma Pfeiffer, Viviane Norris, Shantanu Joshi, Randall Espinoza, Lucina Q Uddin, Katherine L Narr
Imaging neuroscience (Cambridge, Mass.) January 1, 2025 Peer reviewed DOI: 10.1162/imag.a.936 via PubMed
Summary
Ketamine treatment in patients with treatment-resistant depression (TRD) resulted in significant changes in brain network dynamics. After receiving four ketamine infusions, TRD patients showed decreased time spent in the visual network and increased time in the central executive network. Additionally, changes in connectivity patterns between the salience and central executive networks were observed. These alterations were associated with improvements in rumination symptoms, suggesting that ketamine may help normalize brain activity patterns seen in TRD.
Study at a glance
| Design | observational cohort |
|---|---|
| Sample size | 58 |
| Population | patients with treatment-resistant depression |
| Key finding | Ketamine modulates brain network dynamics in TRD, leading to changes associated with improved rumination symptoms. |
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.