BACKGROUND: Depression is a prevalent and debilitating affective disorder characterised by the dominance and persistence of depressive rumination. Mindfulness-based cognitive therapy (MBCT) is an effective treatment for recurrent depression developed specifically to target rumination and recurrence risk by training metacognitive awareness and adaptive attention, emotion and self-regulation skills. Yet, the underlying mechanisms by which mindfulness training impacts maladaptive depressive rumination is not well understood, and a deeper understanding of its effects on the complex brain dynamics during depressive rumination is needed. METHOD: In a randomised controlled functional magnetic resonance imaging (fMRI) study (N = 80), we used LEiDA (Leading Eigenvector Dynamics Analysis) to determine the key substates during resting state fMRI of an experimentally induced rumination state before and after treatment with MBCT (N = 27) for recurrent depression in addition to treatment as usual (TAU) or TAU alone (N = 21). We determined the probability of occurrence (fractional occupancy) and the duration (lifetime) of underlying substates (phase-locking patterns) before and after treatment for both groups. RESULTS: We found that MBCT training compared with TAU altered the fractional occupancy of a 'Salience-somatomotor' substate during the depressive rumination induction. These dynamic network changes in turn were associated with reduced depressive symptoms after treatment and at three months follow up. CONCLUSION: In a depressive ruminative state, changes in the dynamics of the somatosensory-salience network following mindfulness training was associated with improved clinical outcomes which provides insight into candidate brain mechanisms or markers of treatment response.

WK is the Director of the University of Oxford Mindfulness Research Centre. He receives payments for training workshops and presentations related to MBCT and repurposes all such payments to the research programme. WK was, until 2015, an unpaid Director of the Mindfulness Network Community Interest Company and gave evidence to the UK Mindfulness All Party Parliamentary Group. He has received royalties for several books on mindfulness published by Guilford Press. HGR received speaking fees from Lundbeck BV, Wyeth, Janssen, Prelum and Benecke. He obtained funding from ZonMW, Hersenstichting, Parkinson Foundation and unrestricted educational grants from Janssen, all outside of this work. All other authors report no biomedical financial interests or potential conflicts of interest.

NCT03353493

https://www.clinicaltrials.gov/study/NCT03353493

This research was funded by a Carlsberg Foundation Internalization Fellowship (CF21 _ 0645) to AMvdV. JV is supported by EU H2020 FET Proactive project Neurotwin grant agreement no. 101017716. GC was supported by a Research Fellowship from the Netherlands Organization for Health Research and Development (ZonMw, grant number 636320016) and a Brain and Behavior Research Foundation (BBRF) Young Investigator Grant (grant number 29875).

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The Ethics Committee De Videnskabsetiske Komiteer for Region Midtjylland of Central Jutland in Denmark gave ethical approval for this work (protocol number M-2016-259-16)

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