Advanced Functional and Structural MRI Techniques for Neuropharmacological Imaging
Drug Abuse, Nicotine Dependence
About this trial
This is an interventional basic science trial for Drug Abuse focused on measuring Magnetic Resonance Imaging (MRI), Functional Brain Imaging, Magnetic Resonance Spectroscopy, Diffusion Tensor Imaging, Drug Abuse
Eligibility Criteria
- Subjects must be between the ages of 18-80, be generally healthy and male or non-pregnant female. Smokers, non-smokers, drug using and non-drug using populations will participate in this study.
INCLUSION CRITERIA:
General:
- Male and non-pregnant female adults between the ages of 18-80.
- All subjects must be able to provide informed consent.
EXCLUSION CRITERIA:
Subjects will be excluded if they:
- Are pregnant. Urine pregnancy tests will be performed on all female volunteers of child-bearing potential before each experimental session.
- Are unable to undergo MRI scanning due to implanted metallic devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts including Copper 7 IUD) or claustrophobia.
- Are unable to safely undergo TMS stimulation due to having epilepsy or being at high risk for a seizure, being sleep deprived, having a history of unexplained fainting, recurrent severe headaches, significant head injury, having undergone a neurosurgical procedure, having metal in the head, having hearing problems or ringing in the ears or implanted medical devices that could malfunction under TMS stimulation.
- Have major medical illnesses to include, but not limited to, hypertension, cardiovascular disease, asthma, diabetes, peripheral vascular diseases, coagulopathies, syncope, history of superficial or deep vein thrombosis, HIV, or other clinically significant infectious diseases that may alter the signal being measured.
- Have current major psychiatric disorders to include, but not limited to, mood, anxiety, psychotic disorders.
- Have neurological illnesses including, but not limited to, seizure disorders, migraine, multiple sclerosis, movement disorders, or history of head trauma, CVA, CNS tumor.
- Have cognitive impairment as assessed by screening WASI vocabulary subtest below 48, corresponding to full IQ of 85 (in that case on screening, a full WASI will be done to verify IQ of 85 or above).
- Inability to comply with task demands.
- Suspected or confirmed active SARS-CoV-2 infection. Assessment 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) may also be completed. 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. MAI will also retain the ability to exclude for a suspicious symptom screen without positive viral test. 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.
Additional exclusions for some experiments:
Based on the scientific and medical requirements of the particular experiment, participants may also be excluded for:
- left-handedness (if using a cognitive or affective task),
- color-blindness (if using a task requiring color discrimination),
- drug use diagnosis (if a technique is being validated in a non-drug using population),
- renal insufficiency (if contrast agents are to be used), as determined by estimated glomerular filtration rate, which must be > 60 ml/min, as renal insufficiency greatly increases the risk of nephrogenic systemic fibrosis from gadolinium exposure. Renal insufficiency may also be associated with metabolic abnormalities that may interfere with MR imaging.
- Lactation (if contrast agents are to be used). The safety of gadolinium for nursing infants has not been established.
- Use of psychoactive or vascularly active medications (if a functional fMRI technique that is sensitive to hemodynamic changes is being used).
Sites / Locations
- Georgetown UniversityRecruiting
- National Institute on Drug Abuse, Biomedical Research Center (BRC)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
MR Methodology Development and Evaluation
TMS-fMRI Experiment 1
TRPMS Experiment 1
TRPMS Experiment 2
Methodology development and evaluation consists of pulse sequence development, testing, and parameter optimization. For each method we develop or evaluate, we may recruit up to 40 participants to come in for up to 4 visits each. Each participant will be scanned for up to 2 sessions per visit, not to exceed 4 total scan hours per visit.
To evaluate the relationship between BOLD activation and MEP and establish a BOLD activation marker of cortical excitability. Participants will start with a set of two short task-based EPI scans and anatomical scan. RMT will then be determined. Participants will undergo a single-pulse TMS-fMRI scan with stimulation intensities relative to the RMT over the motor cortex and/or the DLPFC. In total, six (6) intensities will be tested, 80% 100%, 105%, 110%, 115%, and 120% relative to the RMT. The fMRI design will be event-related. Each intensity (event type) will be presented 50 times. The order of the intensities will be randomized, and the inter-stimulus-interval (ISI) will range from 12s to 20s (centered at 16s plus random jittering in between, about 0.06Hz). The highest intensity of stimulation will be 120% RMT. EMG recordings in the corresponding hand muscle will be simultaneously acquired during the scan. Total approximate time required for this experiment is about 6-8 hours.
To evaluate the prolonged effect of TPRMS on motor cortex excitability and help interpret and design subsequent experiments investigating the effect of TRPMS on BOLD signal. The experiment design consists of four groups, each group will include 10 participants (8 completers/group). For TRPMS stimulation sessions, our test conditions will be a 10 stimuli-session (approximately 2min), 50 stimuli-session (approximately 7min), 100 stimuli-session (approximately 14min), and 150 stimuli-session (20min) for each of the four groups, respectively. Therefore, the outcome will be measured with the spontaneous motor unit potentials (sMUPs) in the contralateral abductor pollicis brevis muscle (APB). After the stimulation session, we will measure sMUPs continuously for another 20min to observe the prolonged effect of the TRPMS stimulation and to compare these four conditions. The total approximate time required for this experiment is about 2-2.5 hours.
To evaluate cortical excitability changes caused by TRPMS measured with simultaneous TMS-fMRI. Participants will undergo a baseline TMS/fMRI session to get a measurement of baseline cortical excitability in the form of single-pulse TMS induced BOLD activation and determine motor hot-spot and RMT. We will then conduct an event-related single-pulse TMS/fMRI session with TMS stimulus at 120% RMT, 50 events with jittered inter-stimulus-interval (ISI) averaging 16s. Simultaneous EMG recording will be gathered from the corresponding hand muscle. Next we will use TRPMS to stimulate the left motor cortex over the hot-spot : 20-min application of TRPMS, 100ms duration, 0.2Hz (one stimulus every 5s), total 240 stimuli. Then we will evaluate the modulatory effect of the TRPMS stimulation via a second TMS/fMRI session with a similar procedure as the baseline session using the RMT determined at baseline. Total time for this experiment is about 5-6 hours.