The goal of this study is to investigate a new treatment for chronic symptoms after concussion or mild traumatic brain injury in people aged 18-65 years old. Chronic symptoms could include dizziness, headache, fatigue, brain fog, memory difficulty, sleep disruption, irritability, or anxiety that occurred or worsened after the injury. These symptoms can interfere with daily functioning, causing difficulty returning to physical activity, work, or school. Previous concussion therapies have not been personalized nor involved direct treatments to the brain itself. The treatment being tested in the present study is a noninvasive, personalized form of brain stimulation, called transcranial magnetic stimulation (TMS).
The investigators intend to answer the questions:
1. Does personalized TMS improve brain connectivity after concussion? 2. Does personalized TMS improve avoidance behaviors and chronic concussive symptoms? 3. Do the improvements last up to 2 months post-treatment? 4. Are there predictors of treatment response, or who might respond the best?
Participants will undergo 14 total visits to University of California Los Angeles (UCLA):
1. One for the baseline symptom assessments and magnetic resonance imaging (MRI) 2. Ten for TMS administration 3. Three for post-treatment symptom assessments and MRIs
Participants will have a 66% chance of being assigned to an active TMS group and 33% chance of being assigned to a sham, or inactive, TMS group. The difference is that the active TMS is more likely to cause functional changes in the brain than the inactive TMS.
Mild traumatic brain injury (mTBI) defined in accord with the World Health Organization criteria in the last 12 months
age 18-65 at the time of the mTBI
high burden of post-concussive symptoms defined as a score >=20 on the Rivermead Post-Concussion Symptoms Questionnaire
objective neurologic deficits
ongoing or prolonged (>3 months) post-concussive symptoms from a prior mTBI within 2 years of the index injury
history of transcranial magnetic stimulation (TMS) therapy
contraindications for TMS or magnetic resonance imaging (MRI) (e.g., metallic implant other than dental, pacemaker)
Parallel
Active cTBS
Device600 active cTBS pulses will be delivered continuously (3 pulses at 50 hertz (Hz), repeated at 5 Hz, 15 pulses/sec, continuously for 40 seconds) twice/day for 1,200 pulses/day. The MagVenture MagPro active/sham system will be used to enable double blinding by universal serial bus (USB) key in which a current will be delivered through surface electrodes on the skin beneath the coil to mimic the sensory experience of cTBS for active and sham groups.
Inactive/Sham cTBS
Device600 inactive, or sham, cTBS pulses will be delivered continuously (3 pulses at 50 hertz (Hz), repeated at 5 Hz, 15 pulses/sec, continuously for 40 seconds) twice/day for 1,200 pulses/day. The MagVenture MagPro active/sham system will be used to enable double blinding by universal serial bus (USB) key in which a current will be delivered through surface electrodes on the skin beneath the coil to mimic the sensory experience of cTBS for active and sham groups.
Imaginal exposure
BehavioralPersonalized recordings about participants' descriptions of triggering or neutral stimuli or activities
Central target engagement, modulation, and durability
Using resting-state functional magnetic resonance connectivity in the target frontoamygdala circuit
Peripheral target engagement, modulation, and durability
Using heart rate variability as measured by electrocardiogram
Persistent post-concussive symptoms modulation and durability
Using the Modified Rivermead Post Concussion Symptoms Questionnaire where higher scores are worse. Scores range from 0-64.
Fear avoidance modulation and durability
Using the Fear Avoidance Behavior Questionnaire for Traumatic Brain Injury where higher scores are worse. Scores range from 0-48.
Nightly Sleep Score from Oura Ring
Using sleep quality metric, called Sleep Score, from the Oura Ring where higher scores are better, ranging from 0-100.
Daily heart rate variability
Using heart rate variability metric from the Oura Ring
Weekly avoidance behavior
Using a single item question "I avoid activities that might make my symptoms worse" where higher ratings are worse. Ratings range from 1-10.
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University of California, Los Angeles
Lead sponsor
United States Department of Defense
Collaborator
