A non invasive treatment study including participants at risk for suicide attempts and undergoing neurofeedback training. Neurofeedback is controlling your brain activity in real time inside the scanner.
This phased innovation application in response garnered support for an initial (R61) 2-year phase for milestone-driven testing of neural targets of intervention by a novel neurofeedback treatment. Using neurofeedback (NF) we targeted the neurocircuitry of affect regulation and self-processing in adolescents and young adults (ages 11-18) with current significant suicide ideation and a history of a recent suicide attempt. Attaining our the milestones would trigger support for three additional years (R33 phase) to confirm target engagement in a larger sample with random assignment to active NF intervention vs. Placebo NF, to assess the relationships between target engagement and changes in functional outcomes. Affect dysregulation and abnormal self-processing are known to contribute to poor long-term outcomes and predict repeated suicide attempts in at risk populations. They are insufficiently addressed by medications or most existing behavioral treatments. NF training has resulted in enduring improvements in those dimensions in prior Placebo controlled NF trials. To further develop this intervention, we first identified the neural target best engaged by NF during a critical developmental period for affect regulation and self-processing. Our pilot data and theoretical considerations supported the overarching hypothesis that increased amygdala or dACC activity and their functional connectivity (FC) with the middle prefrontal cortex (mPFC) represented treatable targets via NF training. Accordingly, in the initial R61 phase measured intervention-related increases in dACC and right amygdala activity and their FC with mPFC during self-processing and affect regulation tasks with high-quality imaging and clinical data obtained during, before and after NF training. The goal of the R61 phase was to determine which loci is best up-regulated by the targeted population and was best associated with amelioration in the target functional outcomes. If we were to meet our proposed milestones that the increase in dACC or right amygdala and their FC with the mPFC exceeded a specific effect size and account for an appreciable proportion of the variance in behavioral measures of affect regulation and self-processing, we would proceed to the R33 phase. In the R33 phase, we would expand the study to test adolescents randomized to the active NF intervention (dACC or Amygdala) or to a placebo NF who would provide complete high quality pre- and post-intervention and clinical data. We obtained state-of-the-art magnetic resonance imaging (MRI) data with a primary focus on functional MRI. Our specific aims in the R33 phase would be to confirm target engagement in the groups randomized to active vs. the Placebo NF group; to examine the relationship between changes in the neural target and clinical improvements in affect regulation, self-processing and suicide ideation; and to identify mediators of improved functional outcomes. Evidence supporting the validity of dACC or amygdala circuits as a modifiable neural target would then support future studies to further enhance the effectiveness of neurofeedback in adolescents. Importantly, even negative results would be informative regarding the location and direction of neurofeedback (top=dACC vs. down=amygdala) that best attains substantial effects. Inconclusive results from brain imaging would still inform Bayesian priors for future studies of the neural substrates of affect regulation and self-processing impairments and their amelioration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
157
Participants are pseudorandomized to the dACC group to undergo neurofeedback (NF). NF training consists of four \~7.33 min NF training runs preceded by a 5 min baseline (no NF) and followed by a 5 min transfer run (no NF). Training entails NF blocks paired to a self-happy face along a bar that indicates changing levels of the dACC. During the control condition, participants will count backward (CB) from 100 cued by an unfamiliar happy face with no NF. During rest conditions, participants see the cue "Rest" and are asked to relax with their eyes open. During NF, participants will try to increase dACC neural activity by recalling happy memories. The colored bar indicating the neural activity will shift up or down depending on values provided by Turbo-BrainVoyager software. Green = Activity \> baseline and red = Activity \< baseline. Before and after NF training, suicide ideation severity, depression severity, and performance on self-processing behavioral tasks will be assessed.
Participants are pseudorandomized to the rAMY group to undergo neurofeedback (NF). NF training consists of four \~7.33 min NF training runs preceded by a 5 min baseline (no NF) and followed by a 5 min transfer run (no NF). Training entails NF blocks paired to a self-happy face along a bar that indicates changing levels of the rAMY. During the control condition, participants will count backward (CB) from 100 cued by an unfamiliar happy face with no NF. During rest conditions, participants see the cue "Rest" and are asked to relax with their eyes open. During NF, participants will try to increase rAMY neural activity by recalling happy memories. The colored bar indicating the neural activity will shift up or down depending on values provided by Turbo-BrainVoyager software. Green = Activity \> baseline and red = Activity \< baseline. Before and after NF training, suicide ideation severity, depression severity, and performance on self-processing behavioral tasks will be assessed.
University of Minnesota
Minneapolis, Minnesota, United States
Columbia Suicide Severity Rating Scale (CSSRS) - Visit 1
The CSSRS has a scale 0-5 with 0 indicating no suicide ideation and 5 indicating suicide ideation with intent and plan. Higher values are considered the worst outcome The units are ordinal units scored by a clinician following the descriptions in the instrument. Suicidal Ideation Severity Subscale: This core scale has a range of 0 to 5. 0 = No suicidal ideation 1. = Wish to be dead 2. = Non-specific active suicidal thoughts 3. = Active suicidal ideation with method (not plan) 4. = Active suicidal ideation with some intent (no specific plan) 5. = Active suicidal ideation with specific plan and intent
Time frame: Day 0
Columbia Suicide Severity Rating Scale (CSSRS) - Visit 4
The CSSRS has a scale 0-5 with 0 indicating no suicide ideation and 5 indicating suicide ideation with intent and plan. Higher values are considered the worst outcome The units are ordinal units scored by a clinician following the descriptions in the instrument. Suicidal Ideation Severity Subscale: This core scale has a range of 0 to 5. 0 = No suicidal ideation 1. = Wish to be dead 2. = Non-specific active suicidal thoughts 3. = Active suicidal ideation with method (not plan) 4. = Active suicidal ideation with some intent (no specific plan) 5. = Active suicidal ideation with specific plan and intent
Time frame: Week 11
Columbia Suicide Severity Rating Scale (CSSRS) - Visit 5
The CSSRS has a scale 0-5 with 0 indicating no suicide ideation and 5 indicating suicide ideation with intent and plan. Higher values are considered the worst outcome The units are ordinal units scored by a clinician following the descriptions in the instrument. Suicidal Ideation Severity Subscale: This core scale has a range of 0 to 5. 0 = No suicidal ideation 1. = Wish to be dead 2. = Non-specific active suicidal thoughts 3. = Active suicidal ideation with method (not plan) 4. = Active suicidal ideation with some intent (no specific plan) 5. = Active suicidal ideation with specific plan and intent
Time frame: Week 16
Suicide Ideation Questionnaire (SIQ) - Visit 1
Total Suicide Ideation. The suicide ideation questionnaire is a self report measure, higher values indicatemore severe suicide ideation. The total score can range between a minimum of 0 to a maximum 180 (for the 30-item version). A sum of 41 or higher is a common cut-off score indicating the need for further evaluation. Higher scores mean a worse outcome
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Time frame: Day 0
Suicide Ideation Questionnaire (SIQ) - Visit 4
Total Suicide Ideation. The suicide ideation questionnaire is a self report measure, higher values indicatemore severe suicide ideation. The total score can range between a minimum of 0 to a maximum 180 (for the 30-item version). A sum of 41 or higher is a common cut-off score indicating the need for further evaluation. Higher scores mean a worse outcome
Time frame: Week 11
Suicide Ideation Questionnaire (SIQ) - Visit 5
Total Suicide Ideation. The suicide ideation questionnaire is a self report measure, higher values indicatemore severe suicide ideation. The total score can range between a minimum of 0 to a maximum 180 (for the 30-item version). A sum of 41 or higher is a common cut-off score indicating the need for further evaluation. Higher scores mean a worse outcome
Time frame: Week 16
Neural Target Engagement - Visit 2
Activity for the Neural Target indicates level of blood oxigen level dependent activity as obtained via functional magnetic resonance imaging. Higher levels indicate more activity in the area of interest compared to baseline states of the brain.
Time frame: Week 5
Neural Target Engagement - Visit 3
Activity for the Neural Target indicates level of blood oxigen level dependent activity as obtained via functional magnetic resonance imaging. Higher levels indicate more activity in the area of interest compared to baseline states of the brain.
Time frame: Week 8
Difficulties in Emotion Regulation (DERS) - Visit 1
The Difficulties in Emotion Regulation scale is a self-report questionnaire that measures difficulties with emotion regulation. To score the DERS in this study we scored each of the emotion dysregulation scales separately by addidng the items that comprised each scale and dividing the total by the number of items. The total DERS score was calculated by the following formula: COMPUTE ders\_average=MEAN(ders\_difficultygoal\_score,ders\_impulsecontrol\_score, ders\_lackemoclarity\_score,ders\_limaccesstoer\_score,ders\_lowemoaware\_score, ders\_nonacceptance\_score). Higher values indicate more difficulties with emotion regulation. It has a total score range of 9 to 25.33 for the full 36-item version, where higher scores indicate greater difficulty with emotion regulation.
Time frame: Day 0
Difficulties in Emotion Regulation (DERS) - Visit 2
The Difficulties in Emotion Regulation scale is a self-report questionnaire that measures difficulties with emotion regulation. To score the DERS in this study we scored each of the emotion dysregulation scales separately by addidng the items that comprised each scale and dividing the total by the number of items. The total DERS score was calculated by the following formula: COMPUTE ders\_average=MEAN(ders\_difficultygoal\_score,ders\_impulsecontrol\_score, ders\_lackemoclarity\_score,ders\_limaccesstoer\_score,ders\_lowemoaware\_score, ders\_nonacceptance\_score). Higher values indicate more difficulties with emotion regulation. It has a total score range of 9 to 25.33 for the full 36-item version, where higher scores indicate greater difficulty with emotion regulation.
Time frame: Week 5
Difficulties in Emotion Regulation (DERS) - Visit 3
The Difficulties in Emotion Regulation scale is a self-report questionnaire that measures difficulties with emotion regulation. To score the DERS in this study we scored each of the emotion dysregulation scales separately by addidng the items that comprised each scale and dividing the total by the number of items. The total DERS score was calculated by the following formula: COMPUTE ders\_average=MEAN(ders\_difficultygoal\_score,ders\_impulsecontrol\_score, ders\_lackemoclarity\_score,ders\_limaccesstoer\_score,ders\_lowemoaware\_score, ders\_nonacceptance\_score). Higher values indicate more difficulties with emotion regulation. It has a total score range of 9 to 25.33 for the full 36-item version, where higher scores indicate greater difficulty with emotion regulation.
Time frame: Week 8
Difficulties in Emotion Regulation (DERS) - Visit 4
The Difficulties in Emotion Regulation scale is a self-report questionnaire that measures difficulties with emotion regulation. To score the DERS in this study we scored each of the emotion dysregulation scales separately by addidng the items that comprised each scale and dividing the total by the number of items. The total DERS score was calculated by the following formula: COMPUTE ders\_average=MEAN(ders\_difficultygoal\_score,ders\_impulsecontrol\_score, ders\_lackemoclarity\_score,ders\_limaccesstoer\_score,ders\_lowemoaware\_score, ders\_nonacceptance\_score). Higher values indicate more difficulties with emotion regulation. It has a total score range of 9 to 25.33 for the full 36-item version, where higher scores indicate greater difficulty with emotion regulation.
Time frame: Week 11
Difficulties in Emotion Regulation (DERS) - Visit 5
The Difficulties in Emotion Regulation scale is a self-report questionnaire that measures difficulties with emotion regulation. To score the DERS in this study we scored each of the emotion dysregulation scales separately by addidng the items that comprised each scale and dividing the total by the number of items. The total DERS score was calculated by the following formula: COMPUTE ders\_average=MEAN(ders\_difficultygoal\_score,ders\_impulsecontrol\_score, ders\_lackemoclarity\_score,ders\_limaccesstoer\_score,ders\_lowemoaware\_score, ders\_nonacceptance\_score). Higher values indicate more difficulties with emotion regulation. It has a total score range of 9 to 25.33 for the full 36-item version, where higher scores indicate greater difficulty with emotion regulation.
Time frame: Week 16
Responses to Depression (RD) - Visit 1
This questionnaire measures the tendencies to dwell or ruminate about one's symptoms and depression. Higher scores indicate more difficulties with rumination. The score range is 22 to 88, with a total score calculated by summing the responses to its 22 items. Higher scores indicate a greater tendency to respond to sadness with rumination, which can include self-analysis, dwelling on one's anger, or brooding.
Time frame: Day 0
Responses to Depression (RD) - Visit 2
This questionnaire measures the tendencies to dwell or ruminate about one's symptoms and depression. Higher scores indicate more difficulties with rumination. The score range is 22 to 88, with a total score calculated by summing the responses to its 22 items. Higher scores indicate a greater tendency to respond to sadness with rumination, which can include self-analysis, dwelling on one's anger, or brooding.
Time frame: Week 5
Responses to Depression (RD) - Visit 3
This questionnaire measures the tendencies to dwell or ruminate about one's symptoms and depression. Higher scores indicate more difficulties with rumination. The score range is 22 to 88, with a total score calculated by summing the responses to its 22 items. Higher scores indicate a greater tendency to respond to sadness with rumination, which can include self-analysis, dwelling on one's anger, or brooding.
Time frame: Week 8
Responses to Depression (RD) - Visit 4
This questionnaire measures the tendencies to dwell or ruminate about one's symptoms and depression. Higher scores indicate more difficulties with rumination. The score range is 22 to 88, with a total score calculated by summing the responses to its 22 items. Higher scores indicate a greater tendency to respond to sadness with rumination, which can include self-analysis, dwelling on one's anger, or brooding.
Time frame: Week 11
Responses to Depression (RD) - Visit 5
This questionnaire measures the tendencies to dwell or ruminate about one's symptoms and depression. Higher scores indicate more difficulties with rumination. The score range is 22 to 88, with a total score calculated by summing the responses to its 22 items. Higher scores indicate a greater tendency to respond to sadness with rumination, which can include self-analysis, dwelling on one's anger, or brooding.
Time frame: Week 16
Children's Depression Rating Scale - Visit 1
For the Children's Depression Rating Scale-Revised (CDRS-R), which is clinician-rated, the total score ranges from 17 to 113. Higher values indicate a higher severity of child depression. Remission (minimal/no symptoms): \<=28. Moderate to Severe Depression\>=40.
Time frame: Day 0
Children's Depression Rating Scale - Visit 4
For the Children's Depression Rating Scale-Revised (CDRS-R), which is clinician-rated, the total score ranges from 17 to 113. Higher values indicate a higher severity of child depression. Remission (minimal/no symptoms): \<=28. Moderate to Severe Depression\>=40.
Time frame: Week 11
Children's Depression Rating Scale - Visit 5
For the Children's Depression Rating Scale-Revised (CDRS-R), which is clinician-rated, the total score ranges from 17 to 113. Higher values indicate a higher severity of child depression. Remission (minimal/no symptoms): \<=28. Moderate to Severe Depression\>=40.
Time frame: Week 16