Treatment Trials

51 Clinical Trials for Various Conditions

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RECRUITING
Functional Brain Mapping for Patients With Epilepsy
Description

We aim to determine the clinical utility of 'dynamic tractography': a novel method for visualizing electrical neural transfers that incorporates the underlying white matter tracts and supporting linguistic processing. We will also determine how well objective electrophysiology biomarkers will improve the prediction of language outcomes following epilepsy surgery. This project will ultimately optimize understanding of how the human brain develops its language network dynamics.

Conditions
RECRUITING
Non-invasive Brain Mapping of Movement Facilitation in Parkinson's Disease
Description

Several strategies or contexts help patients with Parkinson's disease to move more quickly or normally, however the brain mechanisms underlying these phenomena are poorly understood. The proposed studies use complimentary brain mapping techniques to understand the brain mechanisms supporting improved movements elicited by external cues. The central hypothesis is that distinct networks are involved in movement improvement depending on characteristics of the facilitating stimulus. Participants will perform movement tasks during recording of brain activity with EEG and MRI. The identified biomarkers may provide targets for future neuromodulation therapies to improve symptoms that are refractory to current treatments, such as freezing of gait.

COMPLETED
Precision Functional Brain Mapping in Psilocybin
Description

This project will employ functional brain imaging to study the mechanism and immediate and long-term effects of psilocybin, a serotonin receptor 2A agonist, on cortical and cortico-subcortical brain networks in healthy adults.

Conditions
COMPLETED
Human Brain Mapping of the Apparent Diffusion Coefficient (ADC) During Sleep and Wakefulness
Description

Background: - The glymphatic system helps keep harmful waste from building up in the brain. Researchers think it is more active in people during sleep than while awake. They want to study the glymphatic system using magnetic resonance imaging (MRI). Objective: - To see if there are differences in the way waste is removed from the brain while a person is sleeping versus awake. Eligibility: - Healthy people age 18-60. Design: * This study is in 2 parts. * For the technical part (discontinued), participants will be screened with medical history and physical exam. They will have urine and breath alcohol tests. * Participants will have 2 MRI scans. Before the scans, they will have urine and breath alcohol tests, and complete a questionnaire. * For MRI, participants will lie on a table that slides in and out of a metal cylinder. A device will be placed over their head. They will lie still for up to 20 minutes at a time. They may be asked to stay awake or fall asleep for up to 2 hours at a time. * For the research part, participants will be screened with medical history and physical exam. They will have urine and breath alcohol tests. For 1 week they will wear a device that monitors their activity and sleep. * Participants will stay at NIH overnight. They will give a blood sample, have urine and breath alcohol tests, and complete a questionnaire. * Participants will take memory, concentration, and thinking tests. * Participants will have 3 MRI scans. An electroencephalography machine will record their brain activity. Electrodes will be placed on their scalp.

Conditions
COMPLETED
Brain Mapping of Voice Control
Description

Some voice disorders are caused by uncontrolled muscle actions that affect the larynx or voice box. The purpose of this study is to understand 1) how the brain controls voice production; 2) how changes in sensation within the voice box affect brain control of the voice box; 3) how the central nervous system is affected when people have motor or sensory abnormalities that affect the voice box; and 4) whether patients with voice disorders differ from people without voice disorders in the way the brain controls the voice box. By better understanding these concepts, researchers hope to develop improved treatments for patients with voice disorders. Forty-five healthy adult volunteers and 90 patients with voice disorders will participate in this study. Participants must be between the ages of 20 and 70. The study will involve two visits to the Clinical Center. During the first visit, participants will undergo a medical history and physical exam. During the second visit, investigators will perform the following procedures on study participants: 1) look at the voice box with a nasolaryngoscope, a fine tube through the nose; 2) use MRI \[magnetic resonance imaging\] to record brain activity while participants use their voice to speak; 3) changing sensation in the voice box by dripping a topical anesthetic onto the vocal folds; and 4) using MRI to again record brain activity during speech immediately after applying the topical anesthetic. Participants will receive up to $700 in compensation for their involvement in this study.

Conditions
COMPLETED
Infrared Camera for Brain Mapping During Surgery
Description

It is extremely important to identify and distinguish healthy brain tissue from diseased brain tissue during neurosurgery. If normal tissue is damaged during neurosurgery it can result in long term neurological problems for the patient. The brain tissue as it appears prior to the operation on CT scan and MRI is occasionally very different from how it appears during the actual operation. Therefore, it is necessary to develop diagnostic procedures that can be used during the operation Presently, the techniques used for intraoperative mapping of the brain are not reliable in all cases in which they are used. Researchers in this study have developed a new approach that may allow diseased brain tissue to be located during an operation with little risk. This new approach uses nfrared technology to locate the diseased tissue and identify healthy brain tissue. The goal of this study is to investigate the clinical use of intraoperative infrared (IR) neuroimaging to locate diseased tissue and distinguish it from normal functioning tissue during the operation.

TERMINATED
Brain Areas Involved in Sound and Spoken Word Memory
Description

Background: - Studies have shown that animals such as monkeys and dogs have excellent sight and touch memory but perform poorly on sound memory tasks. Human brains have certain areas that are important for speaking and understanding language. These areas may be involved in sound and spoken word memory. Researchers want to study these areas of the brain to find out if the memory for sounds requires brain structures that are usually associated with language learning and are unique to humans. Objectives: - To use magnetic resonance imaging to study areas of the brain involved in sound memory. Eligibility: - Healthy right-handed volunteers between 18 and 50 years of age. They must be native English speakers and have completed high school. Design: * The study requires a screening visit and 1 or 2 study visits to the National Institutes of Health Clinical Center. * At the screening visit, volunteers will have a medical history taken. They will also have physical and neurological exams, and complete a questionnaire. Women of childbearing age will give a urine sample. Participants who have not had a magnetic resonance imaging (MRI) scan in the past year will have one at this visit. * At the second visit, participants will have tests of sound memory. They will listen to a set of nonsense words spoken through earphones and memorize the words. Then they will listen to the words again to judge if the words were part of the earlier list. Participants will have a 1 hour break, then do the sound memory test again. During the second test they will have repetitive transcranial magnetic stimulation (rTMS), which stimulates different regions of the brain. * If the group results from the testing sessions are positive, there will be a third visit. At this visit, participants will have a sound perception test. They will listen to words spoken through earphones and judge whether the words in the pair are the same or different. Participants will have rTMS during these tests as well.

RECRUITING
Development of Magnetic Resonance Spectroscopic Imaging Techniques for Imaging Metabolites in Human Brain and Muscle
Description

Background: - Magnetic resonance imaging (MRI) is a widely used scanning technique to obtain images of the human body and evaluate activity in the brain. A particular MRI method called magnetic resonance spectroscopy (MRS) can be used to study brain chemistry as well, which may help researchers who are studying new treatments for psychiatric illnesses. Researchers are interested in improving current MRI and MRS techniques, as well as developing new MRI and MRS techniques to view and measure brain chemicals and brain activity. Objectives: - To implement, develop, and optimize brain chemistry imaging techniques using magnetic resonance imaging and magnetic resonance spectroscopy. Eligibility: - Healthy individuals between 18 and 65 years of age. Design: * This study will involve a screening visit and a scanning visit at the National Institutes of Health Clinical Center. * Participants will be screened with a full medical and physical examination, blood and urine tests, and neurological testing. * During the second visit, participants will have an MRI scan of the brain. (Participants who have received an MRI within the past year will not need to have a second one; the images of the previous scan will be used for this study.) All participants will then have an MRS scan using the same scanning equipment.

TERMINATED
Connectivity Analysis for Investigation of Auditory Impairment in Epilepsy
Description

Background: * People with epilepsy often have auditory processing disorders that affect their ability to hear clearly and may cause problems with understanding speech and other kinds of verbal communication. Researchers are interested in developing better ways of studying what parts of the brain are affected by hearing disorders and epilepsy, and they need better clinical tests to measure how individuals process sound. These tests will allow researchers to examine and evaluate the effects of epilepsy and related disorders on speech and communication. * A procedure called a magnetoencephalography (MEG) can be used to measure the electrical currents involved in brain activity. Researchers are interested in learning whether MEG can be used to detect differences in the processing of simple sounds in patients with epilepsy, both with and without hearing impairments. Objectives: - To measure brain activity in hearing impaired persons with epilepsy and compare the results with those from people with normal hearing and epilepsy as well as people with normal hearing and no epilepsy. This research is performed in collaboration with Johns Hopkins Hospital and epilepsy patients must be candidates for surgery at Johns Hopkins. Eligibility: * Individuals between 18 to 55 years of age who (1) have epilepsy and have hearing impairments, (2) have epilepsy but do not have hearing impairments, or (3) are healthy volunteers who have neither epilepsy nor hearing impairments. * Participants with epilepsy must have developed seizures after 10 years of age, and must be candidates for grid implantation surgery at Johns Hopkins Hospital.. Design: * This study will require one visit of approximately 4 to 6 hours. * Participants will be screened with a full physical examination and medical history, along with a basic hearing test. * Participants will have a magnetic resonance imaging (MRI) scan of the brain, followed by a MEG scan to record magnetic field changes produced by brain activity. * During MEG recording, participants will be asked to listen to various sounds and make simple responses (pressing a button, moving your hand or speaking) in response to sounds heard through earphones. The MEG procedure should take between 1 and 2 hours. * Treatment at NIH is not provided as part of this protocol.

COMPLETED
Regional Rates of Cerebral Protein Synthesis: Effects of Sleep and Memory Consolidation
Description

Background: * The brain needs sleep to function normally, but the purpose of sleep is not understood. Brain activity decreases during sleep, so it may be that sleep is important to maintain, repair, or reorganize brain cells. In animals, the formation of brain proteins increases during sleep, and the same thing may happen in humans. * There is also evidence that learning and memory are helped by sleep, and that the synthesis of proteins in the brain are involved. Objectives: * To examine the formation of proteins in the brain while people are awake, deprived of sleep, and during sleep. * To look at the formation of proteins in the brain while awake or asleep and following learning a task. Eligibility: * Healthy volunteers between 18 and 28 years of age. * Volunteers must not have psychiatric, neurologic, or sleep disorders or certain types of vision problems, and must be able to undergo imaging studies. Design: * Study Part I (protein formation in waking, sleep deprivation, and sleep): * Participants will wear an actigraph (a unit to record motor activity) for 2 weeks prior to admission. * Participants will have physical and psychological examinations, along with a blood sample. * After admission participants will have three positron emission tomography (PET) scans to study protein formation and one magnetic resonance imaging (MRI) scan over the course of two days. * Participants may be asked to stay awake for as long as 20 hours and will be monitored throughout. * Participants will be able to sleep overnight after they complete the required scans and monitoring, and will be discharged the following morning. * Study Part II (protein formation in waking and sleep combined with a learning task): * Participants will wear an actigraph (a unit to record motor activity) for 2 weeks prior to admission. * Participants will have physical and psychological examinations, along with a blood sample. * After admission participants may be asked to stay awake for as long as 20 hours and will be monitored throughout. * The next morning, participants will be trained to perform a computerized visual discrimination task, and will be tested 8 hours later (after sleep or after remaining awake) on the visual discrimination task. * Some participants may have PET and MRI scans as part of the study. * Participants will be able to sleep overnight after they complete the required tests and scans, and will be discharged the following morning. * Participants will receive financial compensation for their participation in these studies.

Conditions
COMPLETED
Areas of Brain Responsible for Understanding American Sign Language
Description

The human brain is made up of two halves called hemispheres. Each half of the brain is responsible for processing different kinds of information. Previous neuroimaging studies have shown that both the right and left hemispheres are involved when processing information given in American Sign Language (ASL). However, the study also showed that when processing spoken language, the left hemisphere was mostly involved. Researchers would like to find out more about how the brain processes American Sign Language (ASL). This study is designed to determine if the right hemisphere is necessary for normal understanding of ASL.

COMPLETED
PET Imaging in Chronic Traumatic Encephalopathy
Description

Background: - Chronic traumatic encephalopathy (CTE) is a brain disease caused in part by head injury. The brain changes from CTE can only be seen at autopsy. Researchers want to test a new brain scan to help diagnose CTE in living patients. Objective: - To determine if a new type of brain scan can detect changes that occur in chronic traumatic encephalopathy. Eligibility: - Adults age 18 60 with previous head injury or participation in certain sports. Design: * Participants will be screened with: * Physical exam * Blood and urine tests * Tests of thinking, mood, and memory * 30-minute magnetic resonance imaging (MRI) brain scan. A magnetic field and radio waves take pictures of the brain. Participants will lie on a table that slides into a metal cylinder. They will get earplugs for the loud knocking sounds. * Visit 1: Participants will have a 70-minute PET scan of the brain with a small amount of a radioactive chemical. That will be injected through an intravenous tube (catheter) in each arm. A catheter will also be put into an artery at the wrist or elbow. * Participants will lie on a bed that slides in and out of a donut-shaped scanner. A plastic mask may be molded to their face and head. Vital signs and heart activity will be checked before and during the scan. * Blood and urine will be taken before and after the scan. * Participants will be checked on by phone the next day. * Visit 2: Participants will repeat Visit 1 with a different chemical and no artery catheter. * Visit 3: Participants may have a spinal tap. Some fluid will be removed by needle between the bones in the back.

RECRUITING
Characterization Imaging Instruments in Alcoholics and Non-Alcoholics
Description

Background: - People with alcoholism have differences in their brains compared with healthy people. People who are dependent on alcohol also perform differently on behavioral tasks. Researchers want to find out more about these differences. They also want to see if these differences are related to DNA. Objective: - To see if differences in brain structure relate to personality and behavior differences in people with and without alcohol dependence. Eligibility: - Adults age 18 and older. Design: * Participants will visit the NIH Clinical Center once during the study. * Participants will be screened with a medical history, EKG, and physical exam. They will give blood and urine samples and undergo a psychiatric interview. * Participants will be asked about their alcohol drinking, to see if they have an alcohol use disorder. * Participants will play three computerized games. Some will play these games inside a magnetic resonance imaging (MRI) scanner. * MRI: strong magnetic field and radio waves take pictures of the brain. Participants lie on a table that slides in and out of a cylinder. They will be in the scanner for about 90 minutes. They may lie still for up to 20 minutes at a time. The scanner makes loud knocking noises. They will get earplugs.

SUSPENDED
Estimating Brain Biomechanics Using MRI
Description

Objective: In this study we will develop and apply imaging techniques to perform the first three-dimensional (3-D) measurements of brain biomechanics during mild head movement in healthy human subjects. Biomechanics is the application of mechanics, or the physical principles in action when force is applied to an object, to the anatomical structure and/or function of organisms. Such techniques will be invaluable for building computational models of brain biomechanics, understanding variability of brain biomechanics across individual characteristics, such as age and sex, and determining brain sub-structures at risk for damage when movement of the head is accelerated, such as during a traumatic event. Study Population: Measurements will be performed on 90 healthy men and women aged 18-65. Design: We will build upon the model pioneered by our collaborator, Dr. Philip Bayly. The model places a human subject in a magnetic resonance (MR) scanner with one of two head support units that allows a specific range of motion. Each head support is latched such that it can be released by the subject, and results in either a rotation of the head of approximately 30 degrees or a flexion-extension of the head of approximately 4 degrees. Although both supports are weighted so that the motion is repeatable if the subject is relaxed, the subject can easily counteract the weight. The resulting acceleration/deceleration is small (in the range of normal activities, such as turning one's head during swimming) and has been validated and used in other human investigations of brain biomechanics. The subject repeats the motion multiple times during the MR scan under their own volition and desired pace to measure motion of the head and brain. Outcome measures: This project is a pilot study evaluating the potential of extracting three-dimensional estimates of brain deformation, such as strain measurements, using MR imaging. A primary outcome of this project will be a fast MR acquisition sequence for measuring 3-D brain deformation. The sequence will be evaluated by applying the protocol to human subjects, followed by preliminary quantification of the reproducibility and stability of deformation measurements.

WITHDRAWN
Facilitating Numerical Processing With Transcranial Stimulation in Developmental Dyscalculia
Description

Background: - Developmental dyscalculia is a learning disability in which individuals have difficulty learning or comprehending mathematics or other number concepts (such as keeping score during games, measuring time, or estimating distance). Developmental dyscalculia affects certain parts of the brain that are required for processing numbers. Research has shown that a form of brain stimulation called transcranial direct current stimulation (tDCS), applied when healthy individuals are being trained to carry out tasks with numbers, improved the ability to process numbers and solve math problems. More research is needed about whether tDCS can improve number processing in people with developmental dyscalculia. Objectives: - To examine whether the effects of transcranial direct current stimulation can help individuals with developmental dyscalculia perform mathematical calculations. Eligibility: - Individuals between 18 and 50 years of age who have been diagnosed with developmental dyscalculia, or are healthy volunteers without dyscalculia. Design: * Participants will have a screening visit and seven study visits. The screening visit and six of the study visits will take place consecutively over the course of 6 days, and the final visit will take place 3 months after the initial participation. * Participants will be screened with a medical history, physical and neurological examination, and a brief examination to test for dyscalculia and determine the participant's dominant hand. * Participants will be randomly assigned to one of two groups for the study. One group will receive tDCS during training to perform a task with numbers, and the other group will receive the same training with sham stimulation. Participants will not know which group they are in. * During the study visits, participants will be trained on number tasks on 6 consecutive days. Before the tDCS or sham stimulation is applied at the beginning of the experiment and at the end of each training day, participants will perform other tasks with numbers. Participants will be evaluated based on the accuracy and speed with which they respond to the questions. * At the followup visit, participants will perform the same number tasks they completed during the study visits. No tDCS will be performed at this visit.

RECRUITING
Study of New Magnetic Resonance Imaging Methods of the Brain
Description

The purpose of this investigation is to develop improved magnetic resonance imaging (MRI) techniques and hardware for studying brain function. MRI is a diagnostic tool that provides information about brain chemistry and physiology. This study will evaluate new MRI methods for monitoring blood flow to regions of the brain in response to simple tasks. The MRI machine used in this study is more powerful than those in most hospitals, permitting a higher visual resolution. Normal healthy volunteers over 18 years old may be eligible for this study. Candidates will be screened with a medical history and questionnaire, and a neurological examination. Study participants will have a yearly MRI scan. For this procedure, the subject lies on a stretcher that is moved into a donut-shaped machine with a strong magnetic field. A lightweight circular or rectangular coil a device that improves the quality of the images may be placed on the head. The scan time varies from 20 minutes to 3 hours; most scans last between 45 and 90 minutes. During the scan, the subject may perform simple tasks, such as listening to tapes, tapping a finger, moving a hand, watching a screen, or smelling a fragrance. More complex tasks may require thinking about tones or pictures and responding to them by pressing buttons. Information from this study will be used to develop better imaging methods that will, in turn, permit a greater understanding of normal and abnormal brain behaviors.

COMPLETED
The Connection Between Areas in the Brain of Blind Patients
Description

The purpose of this study is to test the belief that specific areas of the brain are connected differently in blind patients than patients with sight. In addition, the study will examine the different anatomical connections between brain areas of patients who became blind early in life versus patients who became blind later.

COMPLETED
Magnetic Resonance Imaging (MRI) of Neuropsychiatric Patients and Healthy Volunteers
Description

The purpose of this study is to use brain imaging technology to compare differences in brain structure, chemistry, and functioning in individuals with brain and mental disorders compared to healthy volunteers. Schizophrenia is a brain disorder that results from subtle changes and abnormalities in neurons. These deficits likely occur in localized regions of the brain and may result in widespread, devastating consequences. The neuronal abnormalities are inherited through a complex combination of genetic and environmental factors. Brain imaging technologies can be used to better characterize brain changes in individuals with schizophrenia. This study will use magnetic resonance imaging (MRI) scans to identify predictable, quantifiable abnormalities in neurophysiology, neurochemistry and neuroanatomy that characterize schizophrenia and other neurological and neuropsychiatric disorders....

SUSPENDED
Transcranial Magnetic Brain Stimulation to Reduce Cannabis Use in Heavy Cannabis Users
Description

The growing legalization of cannabis across the U.S. is associated with increases in cannabis use, and accordingly, an increase in the number of individuals with cannabis use problems, including cannabis use disorder (CUD). While there are several medications being investigated as treatment options for CUD, none have been FDA-approved, and there is limited efficacy of traditional behavioral therapy approaches for this population. Consequently, there is a pressing need for the development of new treatments, including approaches that specifically target the brain areas associated with problematic cannabis use behaviors. Elevated attention to drug cues is one of the primary causes of relapse in heavy cannabis users. Preliminary data suggests that transcranial magnetic stimulation (TMS), a non-invasive form of brain stimulation, may be a novel brain-based tool to decrease heightened attention to drug cues in people with CUD. Building on prior data, the primary goal of this study is to evaluate the feasibility and effectiveness of TMS as a tool to decrease attention to drug cues and reduce cannabis use. This study will evaluate whether 2 weeks of rTMS can be used to decrease attentional bias to cannabis cues and reduce cannabis use in heavy cannabis users. We will recruit sixty (60) non-treatment seeking, near-daily cannabis users to receive 10 daily sessions of either real or sham (aka placebo) rTMS over a 2-week period. Participants will live on a residential research unit for 3 weeks. During the residential stay, data on cannabis use (measured using standard human laboratory measures of choice to smoke cannabis) and relevant brain activity (measured using drug cue exposure fMRI tasks) will be collected before and after the course of 10 daily rTMS sessions. We will aim to show whether real rTMS treatment reduces brain response and attentional bias to cannabis cues and reduces cannabis use levels.

Conditions
COMPLETED
Handheld Dynamometer During Awake Craniotomy Pilot
Description

The primary purpose of this study is to assess the feasibility, safety and reliability of the use of handheld dynamometry in evaluating intraoperative motor function for patients undergoing awake craniotomy for the resection of brain lesions located within or adjacent to the motor cortex.

TERMINATED
The Entorhinal Cortex and Aerobic Exercise in Aging
Description

The overall goal of this study is to examine how regular exercise affects brain function, spatial memory, and virtual navigation. Participation in this research study will take approximately 4 months.

Conditions
COMPLETED
Neuroimaging Study of Exercise and Memory Function
Description

The investigators are examining the effects of exercise and cardiovascular fitness on cognitive processes, brain function, and the amount of several proteins in the blood. These proteins include a hormone called cortisol, also known as the "stress hormone," and a growth factor called "brain-derived neurotrophic factor" (BDNF). The "stress hormone" cortisol is produced by the adrenal glands. Stress, exercise, obesity, and other factors may influence cortisol levels. BDNF is a protein that promotes the health of nerve cells in the brain and in the body. It plays a role in the growth, maturation, and maintenance of these cells. The amount of this protein in blood samples is therefore an indicator of healthy nerve cell function. Here, the investigators are investigating if exercise improves brain function by changing BDNF levels. Participation in this research study will take approximately 4 months. During this time, participants will make four initial study visits. The first visit is for informed consent and screening, the second and third visits are for baseline fitness testing, and the fourth visit is for a blood draw, cognitive testing, and a functional Magnetic Resonance Imaging (fMRI) exam. Functional MRI is a brain imaging technique that uses a magnetic field to "take pictures" of the brain while a person performs a given task. It will take up to approximately three weeks to complete these initial four study visits. Following the four initial study visits, the exercise-training program will begin. Participants will be randomized to one of two training programs: an aerobic exercise program and a non-aerobic exercise program consisting of strengthening, balance and stretching exercises. The exercise training program will last 12 weeks. There will be three one-hour exercise sessions per week. After completion of the exercise-training program, participants will attend three follow-up study visits. The first two follow-up visits are for fitness testing. The third and final follow-up visit is for a blood draw, cognitive testing, and an MRI exam.

Conditions
RECRUITING
Assessment of Eloquent Function in Brain Tumor Patients
Description

Purpose of the study: AIM 1: Prospectively collect pre-operative \[functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), magnetoencephalography (MEG)\] and intra-operative mapping data in patients with intra-axial brain tumors to assess how well each modality predicts the location of eloquent brain function. In addition, each modality will be compared with the other. AIM 2: Assess reorganization of eloquent brain function and plasticity in patients with intra-axial brain tumors. This will be accomplished by prospectively collecting post-operative mapping studies and neuropsychological tests to compare them to prior mapping studies as stated above.

WITHDRAWN
Using the Digital EEG Spectral Analysis in Assessing Neuroelectrical Processing Abnormalities in Autism
Description

Individuals with Autism Spectrum Disorder will have abnormal DESA® results. Our objective is to use neuroelectrical measures to determine the degree of processing abnormalities in individuals with Autism. The study will survey processing patterns and will locate and evaluate the degree(s) of abnormalities for further study. The abnormal results of comprehensive neuroelectrical evaluations of individuals with Autism when compared to the normative database will provide objective, verifiable, neurophysiological information with which to form novel approaches to the disorder.

COMPLETED
Protein Synthesis in the Brain of Patients With Fragile X Syndrome
Description

Biosynthesis of proteins is essential for growth and continued maintenance of the entire neuron including axons, dendrites, and synaptic terminals, and it is clearly one of the important biochemical processes underlying adaptive changes in the nervous system. Studies in experimental animals with the quantitative autoradiographic L \[1 (14)C\]leucine method have demonstrated a number of the physiological and pathological conditions in which changes in regional rates of cerebral protein synthesis (rCPS) occur. We have recently developed the first fully quantitative method for determining rCPS with positron emission tomography (PET). The PET method was adapted from the autoradiographic L \[1 (14)C\]leucine method; it uses L \[1 (11)C\]leucine as the PET tracer, dynamic scanning, and a kinetic modeling approach for quantification. This method was validated in nonhuman primates by comparison of PET measurements with those based on established biochemical and autoradiographic techniques. The objective of the present study is to examine the degree to which changes in rCPS in human subjects can be quantified with the L \[1 (11)C\]leucine PET method. We propose three studies to be carried out sequentially. In Part I we will establish the L-\[1-(11)C\]leucine PET method in human subjects. In Part II we will measure rCPS in normal control subjects in two states: awake and under deep sedation/general anesthesia with propofol. A difference in rCPS between these two states may indicate that we can detect activity-dependent protein synthesis with the PET method. In Part III we will study subjects with fragile X syndrome. This patient group was chosen since the affected gene in fragile X syndrome codes for a protein that is thought to be a negative regulator of message translation. Thus an effect on protein synthesis may be very close to the underlying genetic abnormality in fragile X syndrome. Regionally selective increases in rCPS have been found in studies in a mouse model of this disease. The present study will establish the sensitivity of the L \[1 (11)C\]leucine PET method to detect changes in rCPS in human subjects. A quantitative and sensitive method to measure rCPS with PET will augment the tools available for investigating the brain and its regional adaptive responses. Ultimately the method may have widespread applications, not only for the study of normal development and plasticity but also in clinical medicine, e.g., in the investigation of disorders of brain development, recovery from brain injury, and neurodegenerative diseases. SPECIFIC AIMS 1. \<TAB\>Establish the L-\[1-(11)C\]leucine PET method for measurement of rCPS in human subjects. Evaluate the optimal scan time and the variability of the measurement in an individual. 2. \<TAB\>Determine the effect of deep sedation with propofol on rCPS in normal human subjects. We will use the \[1-(11)C\]leucine PET method to evaluate lambda, i.e., the fraction of the precursor pool for protein synthesis that is derived from arterial plasma, and rCPS in the same subjects under awake and deep sedation conditions. I)\<TAB\>Hypothesis 1a. Deep sedation with propofol has effects on rCPS. II)\<TAB\>Hypothesis 1b. Deep sedation with propofol has effects on values of lambda. 3. \<TAB\>Assess the sensitivity of the \[1-(11)C\]leucine PET method to detect differences in rCPS in subjects with fragile X syndrome. I)\<TAB\>Hypothesis 3a. There are regionally selective changes in rCPS in subjects with fragile X syndrome compared with age-matched healthy controls. Regions affected include hippocampus, thalamus, hypothalamus, amygdala, and frontal and parietal cortex. II)\<TAB\>Hypothesis 3b. In centrum semiovale, cerebellum, striatum and occipital and temporal cortex rCPS are unchanged in subjects with fragile X syndrome compared with age-matched healthy controls. III)\<TAB\>Hypothesis 3c. Values of lambda in the brain as a whole and in the regions examined are unchanged in subjects with fragile X syndrome compared with age-matched healthy controls. IV) Hypothesis 3d. The average rate of protein synthesis in the brain as a whole is unchanged in subjects with fragile X syndrome compared with age-matched healthy controls.

RECRUITING
Mapping Auricular Vagus Nerve Circuitry
Description

This study will determine how noninvasive nerve stimulation affects human brain, stomach, and autonomic activity.

Conditions
COMPLETED
Magnetic Resonance Imaging of Calculus Problem Solving
Description

This study will use magnetic resonance imaging (MRI) to identify brain regions involved in solving algebraic math problems. It will examine brain activation according to the level of difficulty and the number of steps required to solve the problem. This information will help identify a possible correlation between problem-solving strategies and patterns of brain activation. Undergraduate or graduate students between 19 and 36 years of age who have completed at least 2 years of college, have had at least one college course in integral calculus, and who have no history of neurological disease may be eligible for this study. Candidates will be screened with a medical history, including psychiatric and neurological information. Participants will be asked to mentally solve a variety of integral calculus problems while undergoing MRI scanning, a procedure that uses a strong magnetic field and radio waves to produce images of structural and chemical changes in the brain. During the scan, the subject lies on a table in a narrow cylinder (the scanner) containing a magnetic field. A problem and possible solution are presented to the subject, who presses a button to verify if the answer is correct. At the end of the test, the participant completes a follow-up questionnaire to determine the problem-solving strategies used.

Conditions
COMPLETED
Language Localization Using Repetitive Transcranial Magnetic Stimulation (rTMS) in Patients With Epilepsy
Description

Repetitive transcranial magnetic stimulation (rTMS) may be able to provide a moderately detailed localization of language functions in the brain. We propose to test the ability of rTMS to locate the substrate of visual naming to a limited area of the temporal lobe in patients with temporal lobe epilepsy before and after surgical resections. The study is expected to yield information on the organization of language in the temporal lobes and how unilateral temporal lobe lesions and lobectomy cause relocation of language mechanisms in the lesioned and in the other hemisphere. It will also be a preliminary step in the development of a clinically useful procedure for locating critical language areas in potential surgical candidates.

COMPLETED
Mapping Brain Glutamate in Humans: Sex Differences in Cigarette Smokers
Description

The proposed study will evaluate sex differences in whole-brain glutamate (Glu), with a focus on the dorsal anterior cingulate cortex (dACC), anterior insula, and thalamus, as well as how it is influenced by sex (males vs. females), smoking state (overnight abstinent vs. sated), and circulating ovarian hormones (estrogen and progesterone) in women. Glu will be measured in almost the entire brain, with special focus on the dorsal anterior cingulate cortex (dACC), anterior insula, and thalamus, all of which have been implicated in behavioral states linked to tobacco withdrawal, using an echo-planar spectroscopic imaging (EPSI) variant of magnetic resonance spectroscopy (MRS). Serum ovarian hormones (estrogen and progesterone) will be measured for female participants to determine relationships between brain Glu and this hormone. Whole-brain Glu will be measured in 60 smokers (30 men, 30 women) twice, after overnight (\~12 h) abstinence and after participants smoke the first cigarette of the day.

RECRUITING
Electrocorticography in Mapping Functional Brain Areas During Surgery in Patients With Brain Tumors
Description

This pilot clinical trial studies how well electrocorticography works in mapping functional brain areas during surgery in patients with brain tumors. Using a larger than the standard mapping grid currently used during brain tumor surgery or a high-definition grid for electrocorticogram brain mapping may help doctors to better identify which areas of the brain are active during specific limb movement and speech during surgery in patients with brain tumors.