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 preprint DOI: 10.64898/2026.06.26.26356643 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial |
|---|---|
| Sample size | 80 |
| Population | Patients with major depressive disorder |
| Interventions | Mindfulness-based cognitive therapy treatment as usual |
| Topics | Depression Meditation |
| Keywords | Rumination Mindfulness-based cognitive therapy Cognition Flexibility engineering Cognitive psychology Psychotherapist Mood |
| Key findings | Mindfulness-based cognitive therapy, compared to treatment as usual alone, was associated with greater integration of bodily and interoceptive processing regions within whole-brain manifolds and increased brain flexibility during rumination. |
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.
Comparable studies
Other randomized controlled trials on depression, most cited first.