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Posterior cingulate cortex downregulation training using fMRI neurofeedback in adolescents with early life adversity exposure: a randomized, single-blind trial.

Xiaoqian Yu, Aki Tsuchiyagaito, Masaya Misaki, Gabe Cochran, Zsofia P Cohen, Manpreet K Singh, Martin P Paulus, Robin L Aupperle, Namik Kirlic

Translational psychiatry July 13, 2025 DOI: 10.1038/s41398-025-03445-w

Summary

Early life stress can disrupt brain networks tied to emotional regulation. A study explored if mindfulness, combined with real-time brain activity feedback, could help adolescents manage these networks. Participants practiced mindfulness with feedback on a key brain region. All reported increased mindfulness. Crucially, adolescents with early life adversity showed marked improvements in stress, positive and negative affect. This highlights mindfulness as a powerful, accessible tool for emotional well-being, suggesting its benefits may stem from the core practice rather than enhanced neurofeedback.

Abstract

Early life adversity (ELA) disrupts default mode network (DMN) integrity subserving self-referential processes involved in emotional awareness and regulation. Mindfulness training (MT) reduces self-referential processing and down-regulates the DMN. We employed neurofeedback-augmented mindfulness training (NAMT), combining a core mindfulness strategy (focusing on breath) with real-time fMRI neurofeedback (rtfMRI-nf) to modulate DMN by targeting the posterior cingulate cortex (PCC). ELA-exposed (ELA; n = 43) and healthy control (HC; n = 40) adolescents completed a scan with three conditions: (a) Focus-on-breath (MT): rtfMRI-nf was presented as a variable-height bar, and adolescents attempted to lower the bar; (b) Describe: engaging self-referential processing; and (c) Rest. ELA were single-blind randomized to active PCC rtfMR-nf (NF; n = 22) or artificial feedback (SHAM; n = 21). Adolescents reported perceived stress, state mindfulness, and affect at baseline, post-training, and one-week follow-up. General linear models (GLMs) examined group differences (ELA vs. HC; NF vs. SHAM) on neural (MT vs. Describe) and self-report measures. ELA showed greater difficulty in PCC down-regulation relative to HC. For ELA, SHAM evidenced similar PCC down-regulation as active NF. All adolescents reported increased state mindfulness post-training. Relative to HC, ELA reported greater improvements in positive affect, negative affect and stress at follow-up. There was no difference in self-reported measures between active and SHAM. PCC responses in ELA confirm the region's utility as a potential treatment target. NAMT was feasible and acceptable for ELA-exposed adolescents, but may not enhance mindfulness training more than SHAM. Optimal strategies for enhancing PCC regulation in ELA may be elucidated with future research.

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