Complex harmonic manifolds in mindfulness-based cognitive therapy for major depressive disorder
Paulina Clara Dagnino, Anne Maj van der Velden, Yonatan Sanz Perl, Sara W. Lazar, Henricus G. Ruhé, Jakub Vohryzek, Gustavo Deco, Morten L. Kringelbach
medRxiv July 8, 2026 Peer reviewed DOI: 10.64898/2026.06.26.26356643 via OpenAlex
Summary
Mindfulness-based cognitive therapy (MBCT) may reduce rumination in patients with major depressive disorder (MDD) by enhancing brain flexibility and integrating bodily processing. A randomized controlled trial involving 80 MDD patients revealed that after MBCT, distinct brain patterns emerged that were linked to clinical improvements. These changes suggest that MBCT helps alter ruminative thinking by promoting more adaptable brain dynamics.
Study at a glance
| Design | randomized controlled trial |
|---|---|
| Sample size | 80 |
| Population | patients with major depressive disorder |
| Key finding | After mindfulness-based cognitive therapy, distinct brain patterns associated with clinical improvements and greater flexibility in thinking were observed in MDD patients. |
Abstract
Major depressive disorder (MDD) is a heterogeneous mental disorder characterised by rumination. Mindfulness-based cognitive therapy (MBCT) is an evidence-based treatment developed to target rumination and recurrence risk. Ongoing studies have begun to identify neural changes associated with treatment effects. However, the low-dimensional organisation underlying whole-brain dynamics remains largely unexplored and may provide a more complete characterisation of the neural processes through which MBCT exerts its therapeutic effects in MDD. Here, we investigated functional magnetic resonance imaging (fMRI) of a randomised controlled trial of MBCT with treatment as usual (TAU), or TAU alone, in a group of MDD patients (N=80). We applied a novel framework, complex harmonics decomposition (CHARM), to uncover low-dimensional manifolds in the spacetime domain, capturing local as well as non-local interactions made possible by brain criticality and amplified by the anatomical long-range connectivity. We successfully identified distinct distributed spatiotemporal manifolds across brain states and outperformed traditional dimensionality reduction techniques. During rumination after MBCT we found consistent recruitment of regions involved in bodily and interoceptive processing integrated within the whole-brain across manifolds, changes in latent configurations associated with clinical and behavioural improvements, and greater flexibility within the reduced space. Integration of bodily and interoceptive processing regions within distributed whole-brain manifolds and greater brain flexibility may be associated with reduced 'stickiness' of ruminative thinking patterns following mindfulness training in depression. Our findings highlight the promise of low-dimensional manifolds and long-range interactions arising from critical brain dynamics in understanding how mindfulness targets depressive ruminative processing.