Mindfulness-Based fMRI Neurofeedback for Depression (mbNF)

Targeting Adolescent Depression Symptoms Using Network-based Real-time fMRI Neurofeedback and Mindfulness Meditation (NIMH); Mindfulness-Based Real-Time fMRI Neurofeedback for Depression (IRB)

In the United States, adolescents experience alarmingly high rates of major depression, and gold-standard treatments are only effective for approximately half of patients. Rumination may be a promising treatment target, as it is well-characterized at the neural level and contributes to depression onset, maintenance, and recurrence as well as predicts treatment non-response. Accordingly, the proposed research will investigate whether an innovative mindfulness-based real-time functional magnetic resonance imaging (fMRI) neurofeedback intervention successfully elicits change in the brain circuit underlying rumination to improve clinical outcomes among depressed adolescents.

Adolescent major depressive disorder (MDD) is common and debilitating. Presently, gold-standard treatments are only effective for approximately half of patients, underscoring the need to develop novel interventions, particularly to target core underlying mechanisms and more effectively treat this recurrent disorder. Rumination, the tendency to perseverate about depressive symptoms, contributes to MDD onset and predicts treatment non-response and relapse. At the neural level, rumination is characterized by elevated functional connectivity within the default mode network (DMN), and similarly, prior research has consistently demonstrated patterns of DMN hyper-connectivity in MDD. Interestingly, mindfulness meditation, which trains attentional focus to the present moment, reduces perseverative thinking, ruminative tendencies, and depression symptoms. Further, our research and others have shown that 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 ruminative tendencies during a depressive episode. That is, MDD symptoms, including reduced motivation, inattention, and lack of self-efficacy, may impede a patient's progress in successfully acquiring and utilizing mindfulness strategies necessary to change perceptions about one's environment and relationships. To directly address this challenge, this project will use real-time fMRI neurofeedback to enhance the acquisition and utilization of mindfulness skills to better target DMN hyper-connectivity, rumination, and depressive symptoms. Specifically, a novel, mindfulness-based, real-time neurofeedback (mbNF) paradigm will be used whereby people observe a visual display of their brain activity and practice mindfulness to volitionally reduce DMN activation. Adolescents (N=90; ages 13-18 years) diagnosed with MDD will complete a ~45-minute mindfulness training outside the MRI scanner. To test target engagement of reducing DMN hyper-connectivity and dosing effects, adolescents will all receive mbNF and changes in brain connectivity will be examined (primary outcome). To examine dosing effects, adolescents will be randomized to receive either a 15- or a 30-minute mbNF session (n=45/dose group). Clinician-administered instruments, self-reports, and smartphone ecological momentary assessment will be used test whether mbNF contributes to a greater reduction in clinician assessed depression symptoms as well as decreased rumination post-treatment (secondary outcomes). As a whole, mbNF is directly in line with precision medicine initiatives, and if successful, could revolutionize clinical care for depressed adolescents.

Prior to neurofeedback, participants will receive 45 minutes of mindfulness training. Participants will then receive mindfulness-based fMRI neurofeedback targeting the default mode network and frontoparietal control network.

DMN connectivity will be assessed via fMRI from post mbNF. Changes in DMN connectivity following mbNF are anticipated.

Self-report of depression symptoms from pre-mbNF assessed through the Mood and Feelings Questionnaire; 33-items with each item ranging from 0-2; Higher scores reflect greater depression

Self-report of depression symptoms from post-mbNF assessed through the Mood and Feelings Questionnaire; 33-items with each item ranging from 0-2; Higher scores reflect greater depression

Self-report of depression symptoms from 1 month after mbNF assessed through the Mood and Feelings Questionnaire; 33-items with each item ranging from 0-2; Higher scores reflect greater depression

Depressive symptoms at baseline assessed via the Children's Depression Rating Scale - Revised, which is a clinician interview of depression symptoms. Scores range from 17 to 119 with higher scores reflecting greater depression symptom severity.

Depressive symptoms at 1-month post mbNF assessed via the Children's Depression Rating Scale - Revised, which is a clinician interview of depression symptoms. Scores range from 17 to 119 with higher scores reflecting greater depression symptom severity.

Self-report of rumination symptoms pre-mbNF assessed through the Ruminative Response Scale; 22-items with each item ranging from 1-4; Higher scores reflect greater rumination

Self-report of rumination symptoms from post-mbNF assessed through the Ruminative Response Scale; 22-items with each item ranging from 1-4; Higher scores reflect greater rumination

self-report of rumination symptoms 1-month post mbNF assessed through the Ruminative Response Scale; 22-items with each item ranging from 1-4; Higher scores reflect greater rumination

Change in self-report of depressive symptoms from baseline to post-mbNF assessed through the Patient Health Questionnaire (PHQ)-2 delivered via ecological momentary assessment over a 7-day period; 2-items with each item ranging from 0-100; Higher scores reflect greater depression severity.

Change in self-report of depressive symptoms from baseline to 1-month post-mbNF assessed through the Patient Health Questionnaire (PHQ)-2 delivered via ecological momentary assessment over a 7-day period; 2-items with each item ranging from 0-100; Higher scores reflect greater depression severity.

Change in self-report of rumination (5-items) from baseline to post-mbNF assessed via ecological momentary assessment over a 7-day period; 5-items with each item ranging from 0-100; Higher scores reflect greater rumination.

Change in self-report of rumination (5-items) from baseline to 1-month post-mbNF assessed via ecological momentary assessment over a 7-day period; 5-items with each item ranging from 0-100; Higher scores reflect greater rumination.

Change in self-report of mindfulness (3-items) from baseline to post-mbNF assessed via ecological momentary assessment over a 7-day period; 3-items with each item ranging from 0-100; Higher scores reflect greater mindfulness.

Change in self-report of mindfulness (3-items) from baseline to 1-month post-mbNF assessed via ecological momentary assessment over a 7-day period; 3-items with each item ranging from 0-100; Higher scores reflect greater mindfulness.

Anticorrelation between DMN and FPCN will be assessed via fMRI from pre and post mbNF. Changes in DMN-FPCN anticorrelation are anticipated.

Inclusion Criteria: Ages 13-18 years-old Written informed assent/consent and parental/guardian permission for 13-17 year-olds or informed consent for 18 year-olds Tanner puberty stage ≥3 Meets current diagnostic criteria for MDD English fluency Exclusion Criteria: Lifetime history of primary psychotic disorders, bipolar disorder, oppositional defiant disorder, conduct disorder, developmental disorder (e.g., autism), post-traumatic stress disorder, or eating disorders Substance use disorder, moderate or severe in past 6 months Active suicidal ideation with a specific plan History of seizure disorder Medical or neurological illness (e.g., severe head injury) MRI contraindications Current psychotropic medication use other than antidepressant medication Intelligence quotient (IQ) <80.