Effect of network-based real time neurofeedback augmentation of mindfulness practice on recurrent negative thinking in adolescents at risk for serious mental illness

The National Institute of Mental Health (NIMH) awarded Massachusetts General Hospital a $1.46M Project Grant under the Mental Health Research Grants program (CFDA 93.242) on September 15, 2025, to develop and implement a novel therapeutic intervention combining real-time functional magnetic resonance imaging (fMRI) neurofeedback with mindfulness-based training to address repetitive negative thinking (RNT) in adolescents at risk for serious mental illness. The 24-month project will deliver a Mindfulness-Based Neurofeedback (MBNF) paradigm whereby participants observe visual displays of their own brain activity in the default mode network while practicing mindfulness techniques to volitionally reduce neural hyperconnectivity patterns associated with RNT and transdiagnostic psychiatric symptoms. This intervention targets a critical gap in mental health treatment, as mindfulness meditation alone may prove insufficient for some adolescents whose RNT and mental health symptoms impede successful acquisition of mindfulness strategies.

The grant funds research and development activities designed to enhance adolescents' ability to acquire and utilize mindfulness skills through direct neurofeedback augmentation, with the ultimate goal of improving treatment outcomes in this at-risk population. Products anticipated from this award include empirical validation of the MBNF approach, methodological advances in real-time neuroimaging feedback applications, clinical outcome data regarding RNT symptom reduction, and peer-reviewed publications advancing understanding of transdiagnostic intervention mechanisms in early-onset serious mental illness. Massachusetts General Hospital's Research Management Division will oversee program execution at the awardee's Boston, Massachusetts facility through September 14, 2027.

Abstract

Increasing numbers of adolescents are presenting for mental health care with symptoms consistent with such serious mental illnesses (SMI) as schizophrenia and depression. Many SMI exhibit pluripotent risk profiles during the prodromal phase, underscoring the need to develop novel interventions that target transdiagnostic mechanisms and ameliorate distressing symptoms in adolescents at risk for SMI. Repetitive negative thinking (RNT), maladaptive, repetitive, intrusive, unproductive thought patterns, are associated with a broad range of SMI, and with symptom severity, treatment non-response and relapse. At the neural level, RNT is characterized by elevated functional connectivity within the default mode network (DMN), and similarly, prior research has consistently demonstrated patterns of DMN hyperconnectivity in SMI. Interestingly, mindfulness meditation, which trains attentional focus to the present moment, reduces RNT. Adolescents can apply mindfulness practices to decrease perceived stress, increase sustained attention, and suppress DMN activity. Although mindfulness has profound mental health benefits, for some, mindfulness alone may not be sufficient to mitigate RNT because RNT itself and other mental health symptoms may impede progress in successfully acquiring and utilizing mindfulness strategies. To directly address this challenge, we propose using real-time fmri neurofeedback to enhance the acquisition and utilization of mindfulness skills to better target DMN hyperconnectivity and transdiagnostic RNT symptoms. In our previous research, we developed a novel, 15-minute mindfulness-based, real-time neurofeedback (mbnf) paradigm whereby people observe a visual display of their brain activity and practice mindfulness to volitionally reduce DMN activation. In the R61 phase, 50 at-risk adolescents and 50 healthy control adolescents (ages 13-16) will receive a localizer resting state scan. We will first confirm at-risk adolescents exhibit higher DMN connectivity than controls (go criterion 1). At-risk adolescents will be further randomized to receive a 15- or 30-minute 'dose' of mbnf (n=25/group). We predict reduced DMN connectivity across doses (target engagement; go criterion 2). We also predict at-risk adolescents will show greater reduction of DMN hyperconnectivity after 30 minutes of mbnf compared to 15 minutes. In the R33 phase, a new sample of 90 help seeking adolescents (ages 13-16) with RNT will participate in a double-blind randomized controlled trial of two sessions of either active or sham mbnf (n=45/group) added to mindfulness training. We will test-using clinician-administered instruments and self-reports -whether two sessions of active mbnf compared to two sessions of sham mbnf contributes to a greater reduction in RNT (primary outcome) and psychiatric symptom severity (secondary outcomes) across the 1-month, 3-month and 1-year assessments. As a whole, mbnf is directly in line with precision medicine initiatives, and if successful, could revolutionize clinical care for at-risk adolescents.