Effect of Mindfulness-based Neurofeedback for Adolescents With Elevated Repetitive Negative Thinking

Overview

This study will test the hypotheses that adolescent with repetitive negative thinking who at at-risk for serious mental illness will show greater default mode network (DMN) connectivity than healthy controls, at-risk adolescents will show greater changes in DMN connectivity than healthy controls, and that a longer session of mindfulness based neurofeedback will lead to greater reduction in DMN connectivity. To do so, 50 adolescents with elevated repetitive negative thinking and 50 matched healthy control participants will be enrolled into a double-blind randomized clinical trial of a session of mindfulness training with either active mindfulness-basde neurofeedback or sham mindfulness-based neurofeedback.

Detailed description

A sample of 50 at-risk adolescents with elevated repetitive negative thinking and 50 matched healthy control participants, ages 13-21, will be enrolled into this double blind, randomized clinical trial. Healthy control participants will be matched for age and sex. All participants will complete a baseline clinical assessment and return within two weeks for a brief resting state MRI scan to assess default mode connectivity (DMN). At Visit 2, at-risk adolescents will then receive a 45-minute mindfulness training by clinically trained staff. After the mindfulness training, participants will be randomized in a 1:1 ratio to receive either active or sham neurofeedback. Participants and staff will remain blind to assignment. Participants will have fMRI scans for resting state functional connectivity before and after mindfulness practice. Participants will complete two doses (15 minutes per dose) of real or sham mbNF in the scanner. At-risk adolescents will also complete a follow-up clinical assessment at 4-weeks post-scan (Visit 3) and complete daily surveys for approximately four weeks from Visit 2 to Visit 3.

Interventions

• Behavioral Mindfulness Training
  A single 45-minute mindfulness training will be provided to all at-risk participants at visit 2. Clinically trained study staff will conduct the training with the aim of teaching "mental noting," a core mindfulness technique to be practiced and employed during neurofeedback. Mental noting is a major component of Vipassana (insight mindfulness meditation); its key principles include: "concentration", "observing sensory experience,'' "not 'efforting'", and "contentment".Specifically, participants
• Behavioral Mindfulness-based Neurofeedback (Real mbNF)
  Before the MRI scan, participants will practice mental noting by verbalizing their mental label, with the study clinician providing feedback. Participants will then complete a silent practice of mental noting while viewing simulated neurofeedback. All participants will be trained until they feel competent to use mental noting in the scanner. Study clinicians will show 85% fidelity on the mindfulness training assessment before working with participants and sessions will be recorded and 10% of ses
• Behavioral Sham mindfulness-based neurofeedback (Sham mbNF)
  During sham mbNF condition, participants will undergo similar MRI scan procedures. The primary difference in scan procedures is that rather than receiving mbNF, participants will view a visual display (i.e., white dot, red and blue circles) extracted from a previously acquired mbNF session. Thus, the visual display will be independent from brain activity in the sham condition and will simply mirror the stimuli observed by those in the mbNF group. This ensures that participants across groups are

Primary outcome measures

• Resting State Default Mode Network (DMN) Functional Connectivity [Time frame: Baseline]
• Change in Within-Person Default Mode Network (DMN) Functional Connectivity [Time frame: Pre-mbNF, Post-mbNF (30 minutes after pre-mbNF)]
• Time Effect on Within-DMN Connectivity [Time frame: Pre-mbNF, First post-mbNF (15 minutes after pre-mbNF), Second post-mbNF (30 minutes after pre-mbNF)]

Eligibility criteria

Inclusion criteria

• Ages 13-21, inclusive
• If <18 years old: Competent and willing to provide written informed assent AND have a parent/legal guardian who is competent and willing to provide written informed consent
• If age ≥18 years: Competent and willing to provide written informed consent
• Tanner puberty stage ≥3 (to minimize neuroendocrine variability)
• Able to understand study procedures, read, and write in English
• Access to a mobile device to complete daily surveys

Additional Inclusion Criteria for At-Risk Adolescents - Recurrent negative thinking, defined as PTQ/PTQ-C total score >30 with at least two items rated as 3 (Often) or 4 (Almost Always)

Additional Inclusion Criteria for Healthy Controls

-PTQ/PTQ-C total score <15, with zero items rated as 3 (Often) or 4 (Always)

Exclusion criteria

• Any of the following lifetime mental health disorders by DSM-V criteria: psychotic disorders, bipolar disorder, recurrent moderate or severe major depressive disorder, conduct disorder, developmental disorder (e.g., autism), post-traumatic stress disorder, or obsessive compulsive disorder
• Severe lifetime substance use disorder
• Unstable medical or neurologic condition as determined by study staff, history of epilepsy or seizure disorder, head injury, loss of consciousness >5 minutes by participant self-report
• MRI contraindications (i.e. presence of ferromagnetic implants, cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, magnetic dental implants claustrophobia).
• Visual, auditory, or cognitive impairment (IQ<80 based on the Wechsler Abbreviated Intelligence Scale (WASI)) that may make it difficult to participate.
• Any condition or situation that would, in the investigator's opinion, make it unlikely that the participant could adhere safely to the study protocol.
• Pregnancy: a negative pregnancy test is required at the time of enrollment for any individuals of childbearing potential
• Individuals who are under the legal protection of the government or state (Wards of the State)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

United States · 1 center

• Massachusetts General Hospital, Center for Addiction Medicine, 101 Merrimac Street, Suite — Boston

Identifiers

NCT: NCT07055217 · 2025P001338 · R61MH139856

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗