30 Clinical Trials for Various Conditions
This study will investigate the how the cerebellum is involved in speech motor learning over time and short-term corrections in patients with cerebellar ataxia and healthy controls. This will be accomplished through three approaches: behavioral studies, magnetic resonance imaging (MRI), and transcranial magnetic stimulation (TMS). During behavioral studies, participants will be asked to speak into a microphone while their voice is played back over earphones, and to do other speaking tasks. MRI will be acquired to perform a detailed analysis on brain function and anatomy related to speech and the cerebellum. In healthy controls, TMS will also be performed to temporarily disrupt the cerebellum before, during, or after the participant performs speaking tasks. Patients with cerebellar ataxia and healthy volunteers will be asked to complete behavioral studies and/or MRI; healthy volunteers may be asked to additionally participate in TMS.
This study will evaluate whether applying electrical stimulation on the cerebellum (posterior and lower part of the brain) can influence brain excitability and hand movement performance. A new technique became available to stimulate the brain: transcranial direct current stimulation (tDCS), which could improve the ability to learn. Researchers do not know whether applying tDCS over the cerebellum could also influence motor function, and they want to examine changes in brain excitability, by using transcranial magnetic stimulation (TMS). Patients ages 18 to 40 who are not pregnant may be eligible for this study. They will come to NIH for a medical history and completing a questionnaire about memory and attention. There will be five experiments, each up to 5 hours, for about 1 to 5 weeks, in which patients perform tasks like pinching a special device between the thumb and index fingers, or reaching for target objects on the computer screen. Patients will receive mild electrical stimulation over a different part of the head each day. Some experiments are done without the electrical current, but patients will not know which ones are with or without stimulation. There are also short questionnaires about attention, fatigue, and mood, to be completed before, during, and after each experiment. Patients will be connected to an electromyography (EMG) machine, to measure electrical activity of muscles. Electrodes are taped to the skin over one small hand muscle. TMS allows electrical pulses to pass through the brain to stimulate it. TMS is used at the beginning of each experiment to determine the precise location on the scalp of two target areas: cerebellum and motor cortex. TMS is a safe procedure. Discomfort, headache, or nausea can occur, but all symptoms usually go away promptly. During motor learning under tDCS, also a safe procedure, patients sit in a comfortable chair, and the arm and wrist and arm are kept still. Sponge electrodes are applied on the chin, back of the head, neck, collarbone, lateral part of the head, or above the eyebrow. A small electrical current is passed between electrodes. Patients may feel an itching or tingling sensation under the electrodes or see slight light flashes. tDCS is applied for 20 to 30 minutes. A magnetic resonance imaging (MRI) scan, which may also be involved, uses a strong magnetic field and radio waves to obtain images of body organs and tissues. Patients lie on a table in a cylinder and may be asked to lie still for up to 60 minutes at a time. This study will not have a direct benefit for participants. However, knowledge gained may help researchers identify ways to improve movement in people with a brain injury, such as chronic stroke.
The research study is being conducted to better understand parts of the human brain called the cortex, basal ganglia, thalamus, and cerebellum in patients with movement disorders (such as Parkinson's disease, essential tremor, dystonia, or ataxia). These brain structures are involved in movement disorders. This study attempts to better understand the brain electrical activity associated with these disorders, both in patients with and without deep brain stimulation (DBS). Recordings are made from the scalp with a noninvasive electrode and/or through the DBS stimulator if the participant has a stimulator model that is able to sense brain activity. These recordings are analyzed along with measures of movement disorder symptoms to identify brain signal signatures of symptoms.
The purpose of this research study is to investigate the effects of transcranial direct current stimulation (tDCS) on some of the challenges faced by children with Autism Spectrum Disorder (ASD).
The goal of this study is to determine the impact of neuromodulation to the cerebellum on social and executive functions in neurotypical young adults and young adults with autism.
The goal of this study is to use transcranial magnetic stimulation (TMS) to investigate the impact of modulating cerebellar activity on time perception, executive function, and mood and psychotic symptoms in psychosis patients (i.e., schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features). The investigators hypothesize that abnormally reduced activity in the cerebellum contributes to the abnormalities in patients, that cerebellum-mediated disruptions in time perception may partially underlie executive dysfunction and symptoms, and that cerebellar stimulation will normalize disease-relevant outcome measures.
Functional neuroimaging studies have shown that the cerebellum is active during cognitive performance. The investigators hypothesize that stimulation of the cerebellum with transcranial magnetic stimulation will produce brief changes in performance of the task, suggesting that cerebellar activation is necessary for normal cognitive function.
The goal of this research study is to learn how the brain areas that plan and control movement interact with the areas responsible for hearing and perceiving speech in healthy adults and people who have had cerebellar strokes. The main questions it aims to answer are: 1. What regions of the brain's sensory systems show changes in their activity related to speech? 2. To what extent do these regions help listeners detect and correct speech errors? 3. What is the role of the cerebellum (a part of the brain in the back of the head) in these activities? Participants will be asked to complete several experimental sessions involving behavioral speech and related tests and non-invasive brain imaging using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI).
Motor adaptation and generalization are believed to occur via the integration of various forms of sensory feedback for a congruent representation of the body's position in space along with estimation of inertial properties of the limb segments for accurate specification of movement. Thus, motor adaptation is often studied within curated environments incorporating a "mis-match" between different sensory systems (i.e. a visual field shift via prism googles or a visuomotor rotation via virtual reality environment) and observing how motor plans change based on this mis-match. However, these adaptations are environment-specific and show little generalization outside of their restricted experimental setup. There remains a need for motor adaptation research that demonstrates motor learning that generalizes to other environments and movement types. This work could then inform physical and occupational therapy neurorehabilitation interventions targeted at addressing motor deficits.
Parkinson's disease (PD) is the second most common neurodegenerative disorder and affects approximately 1 million people in the United States with total annual costs approaching 11 billion dollars. The most common symptoms of PD are tremor, stiffness, slowness, and trouble with balance/walking, which lead to severe impairments in performing activities of daily living. Current medical and surgical treatments for PD are either only mildly effective, expensive, or associated with a variety of side-effects. Therefore, the development of practical and effective add-ons to current therapeutic treatment approaches would have many benefits. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can affect brain activity and can help make long-term brain changes to improve functions like walking and balance. While a few initial research studies and review articles involving tDCS have concluded that tDCS may improve PD walking and balance, many results are not meaningful in real life and several crucial issues still prevent tDCS from being a useful add-on intervention in PD. These include the selection of stimulation sites (brain regions stimulated) and tDCS electrode placement. Most studies have targeted the motor cortex (brain region that controls intentional movement), but there is evidence that the cerebellum - which helps control gait and balance, is connected to several other brain areas, and is easily stimulated with tDCS - may be a likely location to further optimize walking and balance in PD. There is also evidence that certain electrodes placements may be better than others. Thus, the purpose of this study is to determine the effects of cerebellar tDCS stimulation using two different placement strategies on walking and balance in PD. Additionally, although many tDCS devices are capable of a range of stimulation intensities (for example, 0 mA - 5 mA), the intensities currently used in most tDCS research are less than 2 mA, which is sufficient to produce measurable improvements; but, these improvements may be expanded at higher intensities. In the beginning, when the safety of tDCS was still being established for human subjects, careful and moderate stimulation approaches were warranted. However, recent work using stimulation at higher intensities (for example, up to 4 mA) have been performed in different people and were found to have no additional negative side-effects. Now that the safety of tDCS at higher intensities is better established, studies exploring the differences in performance between moderate (i.e., 2 mA) and higher (i.e., 4 mA) intensities are necessary to determine if increasing the intensity increases the effectiveness of the desired outcome. Prospective participants will include 10 people with mild-moderate PD that will be recruited to complete five randomly-ordered stimulation sessions, separated by at least 5 days each. Each session will involve one visit to the Integrative Neurophysiology Laboratory (INPL) and will last for approximately one hour. Data collection is expected to take 4-6 months. Each session will include walking and balance testing performed while wearing the tDCS device. Total tDCS stimulation time for each session will be 25 minutes.
This study is a clinical trial to determine the safety of inoculating G207 (an experimental virus therapy) into a recurrent or refractory cerebellar brain tumor. The safety of combining G207 with a single low dose of radiation, designed to enhance virus replication, tumor cell killing, and an anti-tumor immune response, will also be tested. Funding Source- FDA OOPD
The Myelin Disorders Biorepository Project (MDBP) seeks to collect and analyze clinical data and biological samples from leukodystrophy patients worldwide to support ongoing and future research projects. The MDBP is one of the world's largest leukodystrophy biorepositories, having enrolled nearly 2,000 affected individuals since it was launched over a decade ago. Researchers working in the biorepository hope to use these materials to uncover new genetic etiologies for various leukodystrophies, develop biomarkers for use in future clinical trials, and better understand the natural history of these disorders. The knowledge gained from these efforts may help improve the diagnostic tools and treatment options available to patients in the future.
Leukodystrophies, and other heritable disorders of the white matter of the brain, were previously resistant to genetic characterization, largely due to the extreme genetic heterogeneity of molecular causes. While recent work has demonstrated that whole genome sequencing (WGS), has the potential to dramatically increase diagnostic efficiency, significant questions remain around the impact on downstream clinical management approaches versus standard diagnostic approaches.
Although there is increasing recognition that the cerebellum is involved in cognition as well as motor function, the manner in which the cerebellum contributes to cognition is uncertain. One theory that might account for both motor and cognitive contributions of the cerebellum is that the cerebellum is involved in sequencing of relevant events or stimuli. Previous experiments have suggested that disruption of the cerebellum impairs the prediction of the next event in a sequence. The present experiment will examine the impact of cerebellar stimulation on brain activation during the performance of both sequence-demanding and non-sequence-demanding tasks.
PRIME-Ataxia is a randomized controlled trial that aims to determine the feasibility and efficacy of an 8-week telehealth intervention of high intensity aerobic exercise prior to balance training compared to an 8-week telehealth intervention of low intensity exercise prior to balance training in people with spinocerebellar ataxias (SCAs). The investigators additionally aim to explore changes in motor skill learning on a novel motor skill task in a sub-group of participants pre and post intervention.
The aim of the research is to improve motor function in people with cerebellar ataxia by using neuroimaging methods and mental imagery to "exercise" motor networks in the brain. The relevance of this research to public health is that results have the potential to reduce motor deficits associated with cerebellar atrophy, thereby enhancing the quality of life and promoting independence.
This project will study the feasibility of motor rehabilitation in people with cerebellar ataxia using real-time functional magnetic resonance imaging neurofeedback (rt-fMRI NF) in conjunction with motor imagery. To do so, data will be collected from healthy adults in this protocol, to be compared with data from cerebellar ataxia participants.
The primary aim is to show balance training improves DCD individual's ability to compensate for their activity limitations, but does not impact disease progression. The second aim is to demonstrate aerobic exercise improves balance and gait in DCD persons by affecting brain processes and slowing cerebellar atrophy.
Parkinson's disease (PD) affects approximately 1 million people in the US, with annual health care costs approaching $11 billion. PD results from a loss of dopamine-producing cells in the brain. This decrease in dopamine is associated with shaking, stiffness, slowness, balance/walking problems, thinking, and fatigue which severely impair activities of daily living. Current medical and surgical treatments for PD are either only mildly effective, expensive, or associated with a variety of side-effects. Therefore, the development of practical and effective therapies would have significant benefits. Transcranial direct current stimulation (tDCS) can influence how the brain works. A review of studies concluded that, overall, tDCS improves walking and balance in people with PD (PwPD). However, these studies had mixed results. For example, most have stimulated the frontal brain areas and all have used intensities of 2 mA (milliamperes; a measure of electrical current strength) or less. However, given the vital role of the cerebellum in walking and balance, and in PD impairments, the cerebellum may represent a more effective brain target. A recent review of studies also recommended performing investigations of higher intensity tDCS (greater than 2 mA), to potentially increase stimulation efficacy. No study has investigated the effects of multiple sessions of cerebellar tDCS on gait and balance in PwPD and none have used tDCS intensities greater than 2 mA. Therefore, there is a critical need to determine if repeated sessions of cerebellar tDCS might improve walking and balance in the short- and long-term.
Spinocerebellar ataxia type 10 (SCA10) is a hereditary ataxia whose ancestral mutation occurred in East Asia. The mutation is likely to have migrated during peopling of American continents from East Asia. We found a specific rare DNA variation associated with SCA10. We test whether this variation played a key role in the birth and subsequent spreading of SCA10 mutation.
The purpose of this study is to better understand the roles the cerebellum, basal ganglia, and thalamus play in motor learning. Patients undergoing High Intensity Focused Ultrasound (HIFU) treatment will be receiving an ablation procedure to their thalamus as a part of their medical procedure. Participation in this study will include completing a behavioral task before and after the procedure to see how motor learning task performance differs with and without the thalamus. Similarly, patients undergoing Deep Brain Stimulation (DBS) treatment will have an electrode implanted in their thalamus as a part of their medical procedures. Participation in this study will include completing the motor learning task performance "on" and "off" thalamic electrical stimulation.
Transcranial focused ultrasound stimulation (tFUS) will be used in this study to functions of the cerebellum in human motor learning. Participants will complete a visuomotor task while receiving stimulation pulses from tFUS. How tFUS stimulation influencing the acquisition and retention of motor memory will be assessed based on group comparison of behavioral measures such as reaching accuracy.
Emerging neuroimaging studies have shown that the cerebellum contributes to different aspects of timing, prediction, learning, and extinction of conditioned responses to aversive stimuli, factors that may be relevant to the success of exposure based behavioral therapy. Our goals are to determine the cerebellar contributions to fear extinction by attempting to modulate key pathways in this process by theta burst stimulation. The long term goal is to lay the foundation for future studies in which neuromodulation is used to augment exposure therapy.
The purpose of this study is to examine whether cerebellar stimulation can be used to improve cognitive deficits and mood in patients with schizophrenia, autism, bipolar disorder, Parkinson's disease, and major depression.
Background: The way alcohol affects brain structure has been widely studied. But the way it affects all parts of the brain is still unknown. Researchers want to use magnetic resonance imaging (MRI) scans to study brain structure and function. They hope this will help them better understand changes that happen in brain regions during treatment of alcohol use disorders. Objectives: To study changes in the brain by using MRI in people with and without alcohol use disorders. To study how brain changes affect gait, balance, cognitive ability, and behavior. To see how the brain recovers when alcohol use stops. Eligibility: People with alcohol dependence who are currently hospitalized in a particular unit at NIH. Healthy volunteers 30 60 years old without an alcohol use disorder. Design: Participants will be screened under a separate protocol. Participants will give a urine sample for a drug test and pregnancy test at each study visit. They will also have to pass a breath alcohol test. At the first visit, participants will have an MRI. The scanner is a metal cylinder in a strong magnetic field. Participants will lie on a table that slides in and out of the cylinder. They will do behavior and memory tasks outside the scanner. They will have gait and balance tested. They will have to stand on both legs, stand on just one leg, and walk in a straight line. They will perform each task with eyes open, then with eyes closed. They will have tests of memory, thinking, and problem solving. Some participants will have a second visit. They will have another MRI and repeat some of the behavior and memory tasks. ...
Gait and balance disturbances are one of the most incapacitating symptoms of Parkinson's disease (PD) (Boonstra et al. 2008). They can cause falls and are therefore associated with the negative spiral of (near) falls, fear of falling, fractures, reduced mobility and social isolation; hence, having a profound negative impact on quality of life (Lin et al. 2012). Originally, symptoms of PD were ascribed to dopamine deficiency and basal ganglia dysfunction (Wu et al. 2013). However, in the last decades it has become clear that other brain structures are also involved in the pathophysiology of PD (Snijders et al. 2011; Stefani et al. 2007). An intriguing, emerging insight is that the cerebellum may be involved in the pathophysiology of PD (Wu et al. 2013). That is, the cerebellum is hyperactive in PD patients during different motor tasks (Yu et al. 2007; Hanakawa et al. 1999; del Olmo et al. 2006). However, whether cerebellar hyperactivity is pathological or compensatory and how it affects gait and balance in PD patients remain open questions. Here, the investigators aim to elucidate the role of the hyperactive cerebellum in gait dysfunction in PD patients by modulating cerebellar excitability with state-of-the-art non-invasive brain stimulation techniques and investigate the effects on gait.
Friedreich's ataxia is characterized by progressive alterations in the function of the cerebellum accompanied by an atrophy of the spinal cord. Although the genetic defect responsible for the disease has been identified more than 15 years ago, objective markers of the pathologic process (i.e., biomarkers) that would allow measuring the effects of potential therapies are still lacking. Moreover, it is still unclear how the malfunction of the cerebellum affects the rest of the brain, and understanding the connectivity and neurochemistry of the central nervous system might yield new insights in the understanding of the disease, in addition to providing potential markers. To address these needs, the investigators aim at utilizing the capabilities of Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS). Using techniques called Diffusion Imaging, resting-state functional MRI, and Proton Spectroscopy (1H MRS), the investigators propose to determine the differences in the connectivity and neurochemistry of the spinal cord and the brain between patients affected by Friedreich's ataxia and healthy controls. The investigators plan on imaging both patients and control subjects using a 3T magnet, a system that although not yet available in all medical facilities, is becoming standard in most hospitals and clinics. The first aim is to scan patients already scanned last year (12-month follow-up). The second aim is to scan patients at an early stage of the disease.
This study will examine the role of certain areas of the brain in blepharospasm, a type of dystonia (abnormality of movement and muscle tone) that causes unwanted or uncontrollable blinking or closing of the eyelids. The study will compare brain activity in healthy volunteers and in people with blepharospasm to find differences in the brain that may lead to better treatments for dystonia. Healthy volunteers and people with blepharospasm who are 18 years of age and older may be eligible for this study. All candidates are screened with a medical history. People with blepharospasm also have a physical examination and blepharospasm rating. Participants undergo transcranial magnetic stimulation (TMS) and electromyography (EMG) in two 4-hour sessions, separated by 1 to 7 days. TMS A wire coil is held on the subject s scalp. A brief electrical current is passed through the coil, creating a magnetic pulse that stimulates the brain. The subject hears a click and may feel a pulling sensation on the skin under the coil. There may be a twitch in muscles of the face, arm or leg. During the stimulation, subjects may be asked to tense certain muscles slightly or perform other simple actions. Repetitive TMS involves repeated magnetic pulses delivered in short bursts of impulses. Subjects receive 60 pulses per minute over 15 minutes. EMG Surface EMG is done during TMS to measure the electrical activity of muscles. For this test, electrodes (small metal disks) are filled with a conductive gel and taped to the skin of the face.
This study will examine whether high-dose intravenous immunoglobulin (IVIG) is safe and effective for treating cerebellar ataxia-degeneration of the cerebellum, the part of the brain responsible for coordinating muscle movements and balance. The disease causes a slowly progressive impairment of speech and balance, with patients often developing slurred speech, tremor, clumsiness of the hands, and walking difficulties (ataxia). IVIG is derived from donated blood that has been purified, cleaned and processed into a form that can be infused. IVIG is an immune suppressant that is routinely used to treat other neurological conditions. Patients 18 years of age and older with hereditary (genetic) or sporadic (unknown cause) cerebellar degeneration may be eligible for this 5-month study. They must have evidence of an immune component to their condition, such as gluten sensitivity or antiganglioside antibodies. Candidates will be screened with a neurological examination, a review of medical records and possibly blood tests. Participants will be randomly assigned to receive infusions of either IVIG or placebo (an inactive substance) through an arm vein once a month for two months. The infusions will be given in the hospital in doses divided over 2 days, each lasting 6 to 10 hours. Before the infusions, patients will undergo ataxia assessments through tests of coordination and balance that may involve finger tapping, walking in a straight line, talking, and eye movements. When the treatment is finished, patients will be followed in the clinic once a month for 3 months for blood tests repeat ataxia assessments to evaluate the effects of treatment.
This study uses magnetic resonance imaging (MRI) to explore the brain activities involved in performing learned automatic movements. Automatic movements are performed without concentrating on the details of the movement. Healthy adult volunteers are eligible for this study. Candidates will have a medical history and brief physical examination and will fill out a questionnaire. Women of childbearing potential will have a urine pregnancy test. Pregnant women will not be enrolled. Participants will perform certain tasks involving movement of the right or left hand while undergoing MRI scanning. They will undergo scanning twice-before and after practicing the movement tasks. Before the second scan, participants will practice the following tasks for 1 week: * Tapping task - subjects use their left index finger to tap a button at a certain frequency. * Sequential movement task - subjects perform sequential finger-tapping movements with their right hand, in which they tap buttons with their fingers at a certain frequency in a 25-second period. There are two sequences of different lengths, referred to as sequence-4 and sequence-12, based on the number of movements in each unit of the sequence. * Visual distraction task - 14-letter sequences consisting of the letters A, G, L, and O will be presented and subjects will be asked to identify the number of times they see a target letter. * Dual tasks - after completing all the above tasks, subjects perform the following dual tasks: Tapping and visual task Sequence-4 finger tap and visual task Sequence-12 finger tap and visual task Tapping and sequence-4 finger tap Tapping and sequence-12 finger tap When the participants can perform the dual tasks correctly 90 percent of the time, the movements will be considered automatic, and the subjects will undergo MRI scanning. MRI uses a magnetic field and radio waves to produce images of the brain. For the procedure, the subject lies still on a stretcher that is moved into the scanner (a narrow cylinder containing the magnet). Earplugs are worn to muffle loud noises caused by electrical switching of radio frequency circuits used in the scanning process. The scan will last about 1.5 hours.