Use of Repetitive Transcranial Magnetic Stimulation to Augment Hypnotic Analgesia
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Fibromyalgia
- Sponsor
- Stanford University
- Enrollment
- 101
- Locations
- 1
- Primary Endpoint
- The Change in Functional Connectivity (FC) Between the Left Dorsolateral Prefrontal Cortex (L-DLPFC) and the Dorsal Anterior Cingulate Cortex (dACC)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The investigators plan to use functional neuroimaging (fMRI) to understand the brain systems affected when hypnosis and hypnotic analgesia are augmented with repetitive transcranial magnetic stimulation (rTMS), a form of non-invasive brain stimulation to 100 people with fibromyalgia, a chronic pain condition. The investigators will measure the effect of rTMS-augmentation on the brain networks underlying hypnotizability, as well as the effect of rTMS-augmentation on hypnotic analgesia networks. The investigators hope to demonstrate that a combination of these psychological and neuromodulatory treatments will be more effective than hypnosis alone, thereby enhancing the depth of hypnosis, range of hypnosis and the efficacy of hypnotic analgesia and hopefully creating a new treatment modality for individuals suffering from pain syndromes such as fibromyalgia pain.
Detailed Description
Overall Study Design. The investigators propose to develop a combinatory approach where an integrative technique (hypnosis) is augmented with a neurotechnology (repetitive transcranial magnetic stimulation). This application seeks to utilize the previously established brain-based mechanisms of both hypnosis and repetitive transcranial magnetic stimulation as biomarkers to assess the potential synergistic mechanism of this combinatory approach. 100 low-moderately hypnotizable subjects with fibromyalgia will be identified. The subjects' response to rTMS-augmentation of hypnosis will be measured. The volunteers will be randomized to active or sham rTMS. Two scan sessions will be performed for each subject, with the first scan session investigating the effect of rTMS-augmentation on hypnosis and hypnotizability (120 min scan session) and the second scan session focused on the effect of rTMS-augmented hypnotic analgesia (120 min scan session). * During the course of the study and upon consultation with the manufacturer, sham setting intensity was lowered to reduce the risk adverse events (e.g., scalp damage). The study will require that participants participate in an in-person screening visit, a screening MRI scan and 2 MRI scan sessions that include the TMS and hypnosis. Experimental design. Before each MRI scan session, participants will undergo a preparation session, where hypnotizability and either psychological testing or experimental pain training will be conducted. Volunteer subjects will then participate in 2 MRI scan sessions on two separate days, each lasting approximately 120 mins. Hypnosis induction procedures. Hypnosis will be induced while the subject is in the scanner though the use of headphones and a pre-recorded induction script. Hypnotic instructions will be standardized, and will involve a simple induction instruction used in our prior research on the brain signature of the hypnotic state and in clinical care. The ability to enter and maintain the hypnotic state through such an induction mechanism in the fMRI environment has been previously demonstrated.
Investigators
David Spiegel
Willson Professor and Associate Chair of Psychiatry & Behavioral Sciences, Director of the Center on Stress and Health, and Medical Director of the Center for Integrative Medicine at Stanford University School of Medicine
Stanford University
Eligibility Criteria
Inclusion Criteria
- •Fulfill 2010 Fibromyalgia Diagnostic Criteria
- •Age 18 - 70
- •Right-handed
- •Agree to and able to have two fMRI scans as well as rTMS sessions
- •Willingness to suspend use of analgesic drugs or cough suppressants for 24 hours prior to the scans
- •Willingness to suspend us of antidepressant drugs for 2 weeks prior to the scans (6 weeks for fluoxetine)
- •Proficiency in English sufficient to complete questionnaires/follow instructions during fMRI assessments
- •US Citizen or resident able to receive payment legally
- •Low-Moderate Hypnotizability in the Hypnotic Induction Profile (score of 0-8)
- •Normal color vision
Exclusion Criteria
- •A medical condition that would contraindicate the use of rTMS
- •Any condition that would contraindicate MRI (like ferromagnetic metal in the body)
- •Pregnancy or breast feeding
- •Any significant neurologic disease, including dementia, multi-infarct dementia, Parkinson's or Huntington's disease, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, history of significant head trauma
- •Current antidepressant use (must be washed out for two weeks prior to starting protocol)
- •Inability to stop taking medication contraindicated with treatment
- •High Hypnotizability in the Hypnotic Induction Profile (score \>8)
- •Any significant psychiatric disorder as identified on the Mini Mental State Exam (Dysthymia not an exclusion criteria)
- •Color blindness
- •Any significant psychiatric disorder as identified on the Mini International Neuropsychiatric Interview
Outcomes
Primary Outcomes
The Change in Functional Connectivity (FC) Between the Left Dorsolateral Prefrontal Cortex (L-DLPFC) and the Dorsal Anterior Cingulate Cortex (dACC)
Time Frame: Baseline and at 15-20 min post-TMS (up to 30 min)
Functional MRI (fMRI) measures changes in oxygenated blood in the brain; at rest these levels fluctuate over time. These fluctuations can be similar between different brain regions. FC is the similarity in fluctuations of these fMRI signals and suggests how strongly two regions communicate with each other. We measured how inhibitory continuous theta-burst stimulation (cTBS) over L-DLPFC changes FC between L-DLPFC and dACC. This was done by estimating z-transformed correlation coefficients (CC) for each voxel (-1 to 1) between the L-DLPFC and dACC pre and post cTBS intervention. Negative FC was assigned to voxels with a weight \< 0, positive FC to voxels with weight\> 0. Total FC includes positive and negative voxels. The change in FC is regarded as the change in the sum of these weighted voxels from pre to post cTBS for total, positive and negative FC, respectively. Greater sums of voxels correspond to more significant levels of coordinated activity (positive, negative, or total).
Secondary Outcomes
- The Change in the Neural Network Underlying Hypnotic Intensity(Baseline and 2 hours)
- Change in Hypnotic Induction Profile Score(Baseline and Immediately post rTMS (up to 30 min))
- Change in The Hypnosis Intensity Scale(Baseline and immediately post rTMS (up to 2 hrs))
- The Change in Functional Connectivity (FC) Within The Neural Network Underlying Conflict Regulation.(Baseline and at 15-20 min post-TMS (up to 30 min))
- The Change in Stroop Performance(Baseline and at 15-20 min post-TMS (up to 30 min))
- Stroop Task(Baseline and at 15-20 min post-TMS (up to 30 min))
- Linear Relationship Between the Change in FC of the VAN to the DMN and the Change in Stroop Performance (Correlation Coefficient) With no Hypnosis Intervention.(Baseline and at 15-20 min post-TMS (up to 1 hr))
- Linear Relationship Between the Change in FC of the VAN to the DMN and the Change in Stroop Performance (Correlation Coefficient) With Hypnosis Intervention.(Baseline and at 15-20 min post-TMS (up to 1 hr))
- Linear Relationship Between the Change in FC of the VAN to the DMN and the Change in Stroop Interference (Correlation Coefficient) With no Hypnosis Intervention.(Baseline and at 15-20 min post-TMS (up to 1 hr))
- Linear Relationship Between the Change in FC of the VAN to the DMN and the Change in Stroop Interference (Correlation Coefficient) With Hypnosis Intervention.(Baseline and at 15-20 min post-TMS (up to 1 hr))
- Change in the Numeric Pain Rating Scale(Baseline and immediately post-rTMS (up to 30 minutes))
- Change in Sense of Agency Rating Scale (SOARS)(Baseline and immediately post-rTMS (up to 30 min))
- Metabolic Alterations in Fibromyalgia (FMS) Defined by Excitatory / Inhibitory Ratio(Baseline Scan (up to 15 min))
- Alterations in Pain Perception in Fibromyalgia(Baseline visit (up to 30 min))
- Linear Regression of Thermal Pain Threshold to Logarithm of E/I Ratio as it Relates to Water in Fibromyalgia (Coefficient of Determination)(Baseline visit (up to 45 min))
- Linear Regression of Thermal Pain Tolerance to Logarithm of E/I Ratio as it Relates to Water in Fibromyalgia (Coefficient of Determination)(Baseline visit (up to 45 min))
- Linear Regression of Thermal Pain Threshold to Logarithm of E/I Ratio as it Relates to Creatine in Fibromyalgia (Coefficient of Determination)(Baseline visit (up to 45 min))
- Linear Regression of Thermal Pain Tolerance to Logarithm of E/I Ratio as it Relates to Creatine in Fibromyalgia (Coefficient of Determination)(Baseline visit (up to 45 min))
- Metabolic Changes in L-DLPFC Pre- and Post-rTMS(Baseline Scan and at 15-20 min post-TMS (up to 30 min))