Major Depressive Disorder Clinical Trial
Official title:
Effect of Amygdala Neurofeedback on Depressive Symptoms and Processing Biases
The purpose of this study is to determine whether upregulating the left amygdala during positive autobiographical memory recall via real time functional magnetic resonance imaging neurofeedback will lead to an improvement in clinician administered ratings of depressive symptoms. The investigators predict that patients with major depressive disorder receiving left amygdala neurofeedback will increase their amygdala response during positive autobiographical memory recall compared to those receiving control feedback from a region not involved in emotional processing and that this ability will be associated with clinically significant improvement.
Major depressive disorder (MDD) is the leading cause of years lived with disability
worldwide. Traditional pharmacological and/or psychological interventions are ineffective in
up to one-half of patients, and treatments (such as electroconvulsive therapy, vagus nerve
stimulation, and deep brain stimulation) available for severely ill patients who do not
respond to standard interventions are invasive, and associated with potentially significant
side effects. Therefore, there is a need to explore and develop novel non-invasive
treatments.
One such non-invasive method is real-time functional magnetic resonance imaging neurofeedback
(rtfMRI-nf), which allows a person to see and regulate the fMRI signal from his or her own
brain. Emerging evidence suggests rtfMRI-nf has clinical utility in reducing symptoms of
chronic pain, tinnitus, and Parkinson's disease. The goal of the current study is to leverage
recent advances in rtfMRI-nf to determine whether this procedure can be adapted as treatment
for MDD. While amygdala activity is exaggerated in response to negative stimuli in MDD,
evidence further suggests that the amygdala response to positive stimuli is attenuated in MDD
and normalizes with remission. Therefore, the target for our rtfMRI-nf procedure is the left
amygdala. Participants will be randomly assigned to receive rtfMRI-nf from either the left
amygdala or the left horizontal segment of the intraparietal sulcus (HIPS; a region not
involved in emotional processing) and to increase the activity within that region to a target
level by thinking of positive autobiographical memories. This neurofeedback condition will
alternate with periods of rest and counting backwards in order to allow participants to
disengage from memory contemplation. A final run without neurofeedback information will be
included to determine whether participants can maintain the learned amygdala elevation during
positive memory recall in the absence of neurofeedback. Participants will complete two
sessions within a one-week period. Clinical ratings will be taken at the time of each scan to
determine whether the amygdala rtfMRI-nf procedure results in improvement of depression
symptoms, and changes within the emotional regulation network that occur with successful
amygdala regulation will be examined. Furthermore, the investigators aim to determine whether
the rtfMRI-nf procedure will alter assessments of emotional processing conducted within three
days prior to, and following completion of, the rtfMRI-nf procedure.
Specific Aim 1: In individuals with MDD, determine the degree to which rtfMRI-nf enhances
voluntary control over neural activity in the amygdala, co-modulates other brain regions
within the emotion regulation circuitry, and alters depressive symptom severity ratings.
- Hypothesis 1.1: MDD participants receiving rtfMRI-nf regarding blood oxygen-level
dependent (BOLD) activity within their amygdala can learn to voluntarily regulate this
activity in response to positive stimuli. MDD participants receiving rtfMRI-nf regarding
left amygdala activity will demonstrate greater activity in this region while
contemplating positive autobiographical memories (AMs) than MDD participants receiving
rtfMRI-nf regarding BOLD activity in the left HIPS, a region not involved in emotion.
- Hypothesis 1.2: The investigators hypothesize enhancing control over the amygdala via
rtfMRI-nf will increase connectivity strengths between the amygdala and prefrontal
regions involved in modulating emotional behavior including the pregenual anterior
cingulate cortex and ventromedial prefrontal cortex.
- Hypothesis 1.3: The investigators hypothesize participants showing the greatest
enhancement of amygdala activity in response to rtfMRI-nf also will show the greatest
improvement in depressive symptom severity ratings at the end of the study.
Specific Aim 2: In MDD patients, determine the degree to which rtfMRI-nf from the amygdala
restores a normative mood-congruent processing bias during the processing of emotionally
valenced stimuli.
- Hypothesis 2.1: During the performance of a backward masking task in which emotional
faces are presented below conscious awareness, the investigators hypothesize MDD
participants will initially show a processing bias toward negative stimuli in the
amygdala that will reverse to a processing bias toward positive stimuli in participants
receiving active vs HIPS rtfMRI-nf
- Hypothesis 2.2: The investigators hypothesize that MDD patients will initially show a
mood-congruent processing bias toward negative stimuli on the P1Vital Emotional Test
Battery that will reverse to a bias toward positive stimuli following amygdala (vs HIPS)
rtfMRI-nf.
Results from this project will lead to new insights into the plastic neurobiological
mechanisms that govern recovery from MDD and promote novel, non-invasive approaches to MDD
treatment.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05537558 -
Precision Medicine for the Prediction of Treatment (PROMPT) Response (PROMPT)
|
||
Terminated |
NCT02192099 -
Open Label Extension for GLYX13-C-202, NCT01684163
|
Phase 2 | |
Completed |
NCT03142919 -
Lipopolysaccharide (LPS) Challenge in Depression
|
Phase 2 | |
Recruiting |
NCT05547035 -
Identification of Physiological Data by a Wearable Monitor in Subjects Suffering From Major Depression Disorders
|
N/A | |
Terminated |
NCT02940769 -
Neurobiological Effects of Light on MDD
|
N/A | |
Recruiting |
NCT05892744 -
Establishing Multimodal Brain Biomarkers for Treatment Selection in Depression
|
Phase 4 | |
Recruiting |
NCT05537584 -
SMART Trial to Predict Anhedonia Response to Antidepressant Treatment
|
Phase 4 | |
Active, not recruiting |
NCT05061706 -
Multicenter Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder
|
Phase 3 | |
Completed |
NCT04479852 -
A Study of the Safety and Efficacy of SP-624 in the Treatment of Adults With Major Depressive Disorder
|
Phase 2 | |
Recruiting |
NCT04032301 -
Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans
|
Phase 1 | |
Recruiting |
NCT05527951 -
Enhanced Measurement-Based Care Effectiveness for Depression (EMBED) Study
|
N/A | |
Completed |
NCT03511599 -
Cycloserine rTMS Plasticity Augmentation in Depression
|
Phase 1 | |
Recruiting |
NCT04392947 -
Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation
|
N/A | |
Recruiting |
NCT05895747 -
5-HTP and Creatine for Depression R33 Phase
|
Phase 2 | |
Recruiting |
NCT05273996 -
Predictors of Cognitive Outcomes in Geriatric Depression
|
Phase 4 | |
Recruiting |
NCT05813093 -
Interleaved TMS-fMRI in Ultra-treatment Resistant Depression
|
N/A | |
Recruiting |
NCT05135897 -
The Neurobiological Fundaments of Depression and Its Relief Through Neurostimulation Treatments
|
||
Enrolling by invitation |
NCT04509102 -
Psychostimulant Augmentation of Repetitive TMS for the Treatment of Major Depressive Disorder
|
Early Phase 1 | |
Recruiting |
NCT06026917 -
Assessing Dopamine Transporter Occupancy in the Patients With Depression Brain With Toludesvenlafaxine Hydrochloride Extended-Release Tablets Using 11C-CFT Positron Emission Tomography (PET)
|
Phase 4 | |
Recruiting |
NCT06145594 -
EMA-Guided Maintenance TMS for Depression
|
N/A |