Understanding the Acute Modulation of Brain Activity by Transcranial Magnetic Stimulation

  • STATUS
    Recruiting
  • End date
    Dec 31, 2023
  • participants needed
    70
  • sponsor
    National Institute on Drug Abuse (NIDA)
Updated on 14 September 2022
fasting
Accepts healthy volunteers

Summary

Background

Transcranial magnetic stimulation (TMS) is form of non-invasive brain stimulation. It is approved to treat depression. TMS may help decrease drug craving. It is important to understand how TMS affects the brain. Such a better understanding would help to design ways to treat drug addiction.

Objectives

To learn how TMS affects the brain when it stimulates an area in the front of the brain. Also, to see how the stimulation affects the area stimulated and other connected areas.

Eligibility

Healthy, right-handed adults ages 18 60 who are non-drug users.

Design

Participants will be screened under protocol 06-DA-N415.

Participants will have at least 3 visits. The first visit will last about 3 hours. All other visits will last up to 6 hours. Participants cannot use drugs or alcohol at least 24 hours before a visit. They cannot have more than half a cup of a caffeinated drink at least 12 hours before a visit.

Each visit will include a brief medical history update, urine test for drugs and pregnancy (if female), a breath test for alcohol and smoking, and questionnaires.

Participants will have a TMS orientation visit. A wire coil will be placed on the head. An electrical current will pass through the coil to create a magnetic pulse that stimulates the brain.

The other visits will include 2 sessions of TMS-MRI. Participants will lie on a table that slides into a cylinder. The TMS coil and the MRI coil will be placed over the head. Pictures will be taken of the brain with and without stimulation.

Participants will complete a questionnaire about how they feel before and after each TMS session and in a follow-up call 2 3 weeks after their last session.

Description

Objectives: The goal of the protocol is to investigate acute modulations of brain activity by transcranial magnetic stimulation (TMS). Using simultaneous TMS and functional magnetic resonance imaging (fMRI), we will evaluate TMS induced changes in brain activity, including regional brain activation and inter-regional functional connectivity. Repetitive TMS will be applied over the dorsolateral prefrontal cortex (DLPFC) with different frequencies and interleaved with fMRI acquisition to provide online monitoring of brain activity. Furthermore, we will assess the relationship between the TMS induced brain activity and the anatomical connection obtained from diffusion tensor imaging (DTI), using individual variations in these imaging measures. Results from this study will help to understand the underling mechanism of TMS and will provide insights for interpretation of TMS and fMRI data. Study population: Up to 70 healthy, adults will be tested. Subjects must fit exclusion/inclusion criteria for both TMS and MRI. We expect to enroll 70 subjects to arrive at 50 who complete the protocol. Design: The study is a within-subject design with each subject completing up to 4 TMS-fMRI sessions in two days (2 sessions per day) Outcome measures: The outcome measures will be the effects of TMS on fMRI blood oxygen level-dependent (BOLD) responses, TMS induced changes on resting state functional connectivity, and their associations with relevant structural connectivity revealed by DTI.

Details
Condition Healthy Volunteers
Treatment TMS, TMS (MagVenture MagPro 100 with MagOption)
Clinical Study IdentifierNCT03394066
SponsorNational Institute on Drug Abuse (NIDA)
Last Modified on14 September 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Subjects must
Be able to give valid informed consent
Be 18 60 years of age
Justification: Many neural processes change with age, and these changes could introduce unwanted variability in both behavioral and MRI signals. In addition, the risk of difficult-to-detect medical abnormalities such as silent cerebral infarcts increases with age
Screening tool: History. Government-issued forms of identification (e.g. driver s license, birth certificate) will be required when participant appears to be out of age range
Be in good health
Justification: Many illnesses may alter neural functioning as well as fMRI signals
Screening tools: Medical Assessment, Medical History and Physical Examination. Medical assessments include: Vital Signs, EKG, oral HIV test, height/weight measurements, urinalysis and blood sample. Tests on the blood sample include CBC, complete metabolic profile, TSH, ESR, STS and HIV (if needed to confirm a positive salivary test for HIV). The following individual laboratory results will independently disqualify individuals: Cholesterol >250 mg/dl, Hemoglobin < 10.5 g/dl, WBC < 2400/ (Micro)l, LFTs > 3Xnormal, HCG positive, Casual serum glucose > 200 mg/dl, Urine protein > 1+. The MAI will retain discretion to exclude at less extreme values, depending on the clinical presentation. (Serum glucose over 140 mg/dl will be followed up with a fasting serum glucose assessment. Those with fasting glucose below 100 mg/dl may be considered for the protocol. Others will be rejected and referred for work-up.) MAI will make the final judgment on any questionable lab results
Right-handed
Justification: Using right-handed individuals will reduce variability in BOLD MRI data
Screening tool: Edinburgh Handedness Inventory

Exclusion Criteria

Personal history of stroke, brain lesions, previous neurosurgery, any personal history of seizure or fainting episode of unknown cause, or head trauma resulting in loss of consciousness, lasting over 30 minutes or with sequela lasting longer than two days
Justification: Stroke or head trauma can lower the seizure threshold, and are therefore contra-indications for TMS. Fainting episodes or syncope of unknown cause could indicate an undiagnosed condition associated with seizures
Screening tool: TMS safety questionnaire, Medical History
First-degree family history of any neurological disorder with a potentially hereditary
basis, including migraines, epilepsy, or multiple sclerosis
Justification: Neurological disorders can lower the seizure threshold, and are therefore contra-indications for TMS. First-degree family history of certain neurological disorders with a hereditary component increases the risk of the subject having an undiagnosed condition that is associated with lowered seizure threshold
Screening tool: TMS safety screening, Medical History
Justification: Any metal around the head is a contraindication for both MRI and TMS, as both methods involve exposure to a relatively strong magnetic field
Cardiac pacemakers, neural stimulators, implantable defibrillator, implanted
Screening tool: TMS safety screening, MRI safety screening, Medical History
medication pumps, intracardiac lines, or acute, unstable cardiac disease, with
Noise-induced hearing loss or tinnitus
intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear
Justification: individuals with noise-induced hearing problems may be particularly vulnerable to the acoustic noise generated by TMS and MRI equipment
implants, or electrodes) or any other metal object within or near the head
Screening tools: TMS safety screening
that precludes MRI scanning
Justification: The use of certain medications or drugs can lower seizure threshold and is therefore contraindicated for TMS
Screening tools: MRI safety screening questionnaire, Medical history, Medical Assessments: Urine toxicology analyzes for presence of a broad range of prescription and nonprescription drugs
Justification: The population of interest here is a healthy control population with no psychiatric disorders. In subjects with depression, bipolar disorder, mania or hypomania, there is a small chance that TMS can trigger (hypo)manic symptoms
Current use (any use in the past 4 weeks, chronic use within 6 past six months) of any
Screening tools: MINI Screen Patient Questionnaire. Potential diagnoses will be further evaluated by a counsellor
investigational drug or of any medications with psychotropic, anti or pro-
Justification: The population of interest here is a healthy control population with no substance use disorder and therefore a minimal cigarette exposure history in the control group is required
convulsive action
Screening tools: Self-report, commercial urine cotinine test corresponding to non-smoker status for the specific test being used, typically corresponding to a urine cotinine under about 20 ng/ml, CO <6\
Justification: The population of interest here is a healthy control population with no substance use disorder. Current use of illicit substances could lower seizure threshold and is therefore contraindicated for TMS
Lifetime history of major depressive disorder, schizophrenia, bipolar disorder, mania
Screening tools: MINI Screen Patient Questionnaire. Potential diagnoses will be further evaluated by a counsellor, Drug Use Survey (DUS), Substance Use Disorder Evaluation, Medical Assessments: urine qualitative drug screen is performed for methadone, benzodiazepines, cocaine, amphetamine/methamphetamine, opiates, barbiturates, and tetrahydrocannabinol. Participants who test positive at screening (under protocol 06-DA-N415) will be evaluated with a neuromotor exam to further assess for current intoxication. For participants who are not found to be currently intoxicated, screening staff will assess for SUD and coherence of their drug use history and toxicology, with particular attention to substances for which they are positive and may require a return screening visit to demonstrate ability to produce a negative urine before allowing them to proceed to clearance for this study
or hypomania
Have met DSM-5 criteria for any substance use disorder in the past
Justification: the population of interest here is a healthy control population with no present or past substance use disorder
Current use of nicotine or history more than 20 cigarettes lifetime or history of
Screening tools: MINI Screen Patient Questionnaire. Potential diagnoses will be further evaluated by a counsellor. Drug Use Survey (DUS), Substance Use Disorder Evaluation
daily smoking
Justifications: the risk of TMS for individuals with a heart condition is unknown
Screening tool: physical assessment (EKG), medical history
Meet current DSM-5 criteria for any substance use disorder, smoke daily, or urine
toxicology positive for any illicit substance inconsistent with history given
Justification: it is unknown whether TMS or MRI poses a risk to fetuses
Screening tool: Medical assessments (urine pregnancy test) at the beginning of each visit that involves TMS or MRI
Participation in an rTMS session less than two weeks ago
Justification: in order to limit exposure to TMS, we will not enroll subjects who have received TMS less than two weeks ago
Screening tool: TMS safety screening questionnaire
History of Learning disability, ADHD or cognitive impairment
History of myocardial infarction, angina, congestive heart failure, cardiomyopathy
Justification: Cognitive impairment and learning disabilities are associated with alterations in brain regions and may introduce significant variably into the data
stroke or transient ischemic attack, or any heart condition currently under
Screening tool: self-report of special education classes, history of specific learning disability or mental retardation, Wechsler Abbreviated Scale of Intelligence (WASI), Medical history and Adult ADHD Self-Report Scale with follow up clinical interview
Non-English Speaking
medical care
Justification: There is no direct benefit to participants in this study, and some of the study procedures involve more than minimal risk. To include non-English speakers, we would have to translate the consent and other study documents and hire and train bilingual staff, which would require resources that we do not have and could not justify given the small sample size for each experiment. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing MRI and TMS procedures. The inability to effectively communicate MRI and TMS safety procedures could compromise the safety of non-English speaking participants
Screening tool: self-report
Pregnant women or women with reproductive potential who are sexually active and not
Suspected or confirmed active SARS-CoV-2 infection
using an acceptable form of contraception
Justification: COVID-19 is extremely infectious and can have serious consequences. Allowing participants with active infection would alter the risk:benefit ratio for non-treatment studies without a primary focus on SARS-CoV-2 to an unacceptable level of risk. In addition, COVID-19 can have cognitive consequences which would add unnecessary noise to the study data. Testing will continue as long as public health officials and/or NIDA medical personnel deem it appropriate
Screening tool: 2019 Novel Coronavirus (COVID-19) patient screening tool administered by phone prior to participant arrival. The current version of the screening tool to be used is available at <http://intranet.cc.nih.gov/hospitalepidemiology/emerging_infectious_diseases.html> ). Viral testing looking for SARS-CoV-2 in a specimen deemed appropriate by NIH such as nasopharyngeal or mid-turbinate swab. We reserve the right to change the specimen type as NIH approves new test procedures. This test may be carried out in-house at NIDA, NIH, at a community testing site or through a commercial vendor. Anyone with a positive symptom screen without a clear alternative explanation or a positive viral test will be excluded until they recover or (for asymptomatic cases) are no longer infectious. Additionally, participants will be asked about any lingering neurological and psychiatric symptoms such as difficulty with memory or concentration, changes in mood or new anxiety symptoms that may be a result of COVID-19 exposure. The MAI will evaluate any lingering symptoms to determine whether the potential impact on data is compatible with continuing in the study. MAI will also retain the ability to exclude for a suspicious symptom screen without positive viral test
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