Synaptic Regulation Impairment

Researchers are studying an experimental therapy to help people recover arm movement after a stroke. This therapy combines functional electrical stimulation with a P-300 based Brain-Computer Interface system BCI-FES to assist arm rehabilitation. The study compares two groups one receives only conventional physical therapy, and the other receives both conventional therapy and BCI-FES. The goal is to improve motor recovery and independence in patients with moderate to severe upper limb weakness due to stroke. Both groups will undergo 20 sessions of conventional physical therapy over 4 weeks, with five sessions each week. The experimental group will also receive 20 sessions of BCI-FES therapy during the same period. The BCI system detects the patients intended hand movements and assists with movements such as hand opening, grasping, pinching, pronation, and supination. These movements are practiced alongside daily tasks using objects like bottles and spoons. The therapy aims to stimulate brain pathways involved in movement to support recovery. Participants will be evaluated before and after the 4-week treatment using tests that measure arm motor function, spasticity, independence, and depression. Brain imaging with MRI and EEG will assess changes in brain structure and activity. Safety and comfort during sessions will be monitored, including fatigue and skin irritation. The total involvement lasts about one month, with close follow-up during therapy and assessments of progress and brain changes.

Researchers are evaluating a new surgical approach called connectome-guided network-based navigation for brain tumor surgery in areas of the brain responsible for important functions, known as eloquent regions. This approach uses advanced diffusion MRI to create personalized maps of the brains white matter pathways and networks. The goal is to see how often this network-based information changes surgical plans compared to traditional anatomy-based methods and to assess early neurological outcomes after surgery. The study involves patients undergoing surgery to remove gliomas or brain metastases located in or near eloquent brain regions. The approach integrates patient-specific brain network maps into clinical neuronavigation systems to guide preoperative planning and decisions during surgery. This includes the use of advanced image processing pipelines and integration with intraoperative monitoring, sometimes combined with awake craniotomy and direct brain stimulation. The surgical team uses these brain maps to plan the craniotomy and the tumor removal while aiming to preserve critical brain functions. Participants undergo preoperative and postoperative MRI scans, including diffusion imaging, and neurological assessments at hospital discharge and three months after surgery. The study measures how often surgical plans change due to network-based information, the presence of lasting neurological deficits at three months, the extent of tumor removal, and the closeness of surgery to important white matter tracts. The feasibility of using this advanced imaging and navigation approach in a busy clinical setting is also evaluated. Participants remain under clinical follow-up at the hospital after surgery.

Researchers are studying the effects of glucagon-like peptide 1 receptor agonists GLP-1 RAs on muscle mass, physical function, and brain signaling related to appetite in adults aged 50 to 75 with obesity and decreased physical function. This study aims to understand how 1 year of GLP-1 RA therapy, with or without exercise training, impacts these outcomes and what happens after stopping the treatment for another year. The study is a randomized clinical trial lasting 2 years. Participants are divided into two groups. One group will receive semaglutide injections once weekly along with diet behavior counseling for 52 weeks. The other group will receive the same semaglutide treatment and diet counseling plus supervised exercise training three days a week and unsupervised sessions 2 to 3 days a week for the same period. After this 1-year treatment period, all participants will stop the GLP-1 medication and exercise if applicable, and their muscle and appetite-related outcomes will be monitored for another year. During the study, participants will have assessments of physical function and body composition at the start, after 52 weeks of treatment, and again 52 weeks after stopping treatment. Additional measures include muscle mass, muscle volume, insulin sensitivity, muscle strength on various exercises, and brain connectivity in a subset of participants. The study includes regular monitoring of these outcomes to evaluate the effects of treatment and cessation over the 2-year period.

Researchers are investigating how mechanical and non-mechanical factors contribute to chronic neck, shoulder, arm, and back pain in full-busted women. This study focuses on women with larger bra cup sizes, exploring how sex hormones, inflammation, and brain changes affect pain. The project aims to fill gaps in understanding pain mechanisms in women with chronic musculoskeletal pain related to breast size. The study evaluates a mechanical intervention using specially designed sports bras for full-busted women cup sizes D to I to see if they help reduce pain. Participants in the intervention group will receive one of two types of interventional sports bras to wear for three months. A control group of women with smaller cup sizes A to C will be observed without receiving the intervention. Both groups will undergo various baseline and follow-up assessments over three months. Participants will complete online and in-person sessions including questionnaires, pain assessments, body measurements, blood tests, and brain imaging at the start and after three months. Physical activity will be monitored using a smartwatch during the study period. Researchers will collect multiple measures to understand pain, activity, hormone levels, inflammation, biomechanics, and brain activity. The study lasts at least three months, with detailed follow-up to assess the impact of the sports bras and related pain pathways.

Researchers are investigating why some adolescents with depression and suicidal thoughts or behaviors act more impulsively when experiencing negative emotions, a trait known as negative urgency. This study aims to explore how this impulsivity relates to brain cell communication, particularly focusing on cortical inhibition in the dorsolateral prefrontal cortex. The study will include adolescents aged 13 to 21 years with depression and either suicidal ideation or suicidal behavior, to better understand the neural mechanisms involved. Participants will undergo assessments at the start of the study, and again at 6 and 12 months. These assessments include clinical interviews, questionnaires about thoughts, emotions, and impulsive behaviors, computerized brain function tests, MRI brain scans, and a specialized brain measurement using single- and paired-pulse transcranial magnetic stimulation with electroencephalography TMS-EEG. Both groups, those with suicidal ideation and those with suicidal behavior, will receive the same evaluations throughout the study. During the study, participants will complete interviews and rating scales to assess their symptoms and negative urgency. Brain physiology related to cortical inhibition will be measured noninvasively using TMS-EEG at each visit. Researchers will track changes in brain signaling and impulsivity over time to understand their relationship. The total duration of participation is 12 months, with key outcome measures including long-interval intracortical inhibition and negative urgency at baseline, 6 months, and 12 months.

Researchers are studying how aerobic endurance training affects patients with schizophrenia, focusing on changes in the brains hippocampus, symptoms, cognition, and daily functioning. The study aims to understand genetic and epigenetic factors influencing brain plasticity after three months of endurance training compared to a control group performing flexibility, strengthening, and balance exercises. The main goal is to examine how a genetic risk score for schizophrenia relates to volume changes in a specific hippocampal region called CA4DG. Participants are randomly assigned to either aerobic endurance training using a bicycle ergometer or to flexibility, strengthening, and balance training. The endurance training starts with three 40-minute sessions per week for six weeks, then three 45-minute sessions per week for the next six weeks, conducted in small groups. The control group performs exercises focusing on stretching, strength, balance, and relaxation, with session durations increasing from 40 to 50 minutes over 13 weeks. During the 13-week study, participants undergo assessments of hippocampal volume, cognitive and executive functions, symptom severity, daily life functioning, and cardiovascular risk factors. The trial includes double-blind monitoring, and all participants receive individualized medication following standard treatment guidelines. The total study period allows researchers to observe brain structure and functional changes related to physical training in schizophrenia.

Researchers are studying children aged 6 to 12 years with and without mathematical learning disabilities to understand the brain and cognitive processes involved in learning numerical skills. This study evaluates how children respond to interventions designed to improve weaknesses in math abilities by enhancing connections between symbolic and non-symbolic number understanding. The research aims to uncover how these changes relate to brain function and learning differences among children. Participants are randomly assigned to one of two groups for a 6-week program. One group receives an integrative symbolicnon-symbolic iSNS training that strengthens the link between symbolic numbers and quantities. The other group completes an active control intervention focusing on improving short-term memory for visual or verbal information. Training involves working on tablet-based activities at home three days a week with weekly one-on-one support from the research team. MRI brain scans and behavioral tests are conducted before and after the intervention, with an additional follow-up assessment six months later to measure lasting effects. Throughout the study, children complete various tasks measuring reaction times and accuracy in symbolic and non-symbolic number comparisons and addition. Researchers also analyze brain activity changes related to these tasks. Assessments include cognitive tests, brain imaging, and tracking of learning progress. The study lasts about six weeks for the intervention, plus follow-up visits after six months to evaluate long-term benefits and brain plasticity.

Researchers are evaluating the antidepressant effects of 2R,6R-hydroxynorketamine HNK in adults with treatment-resistant major depressive disorder MDD. This phase 2 randomized, double-blind, placebo-controlled, crossover study aims to determine if HNK can improve overall depressive symptoms faster than current treatments. The study focuses on adults aged 18 to 70 years with MDD who have undergone a prior screening assessment and experienced inadequate responses to antidepressant therapies. Participants will taper off their current antidepressant medications over 2 to 5 weeks and then remain off these drugs for up to 2 weeks before starting study treatments. They will receive HNK or placebo infusions intravenously through a vein, with four infusions over two weeks during each of two test sessions. One test session involves HNK, and the other involves placebo, with a crossover design where participants receive both treatments in different orders. Doses range from 0.25 mgkg up to 2.0 mgkg, adjusted based on response and tolerability. Participants stay overnight at the clinical center after each infusion or for the study duration. Throughout the trial, participants undergo physical exams, blood tests, heart function assessments, mood and cognitive evaluations, and complete symptom questionnaires. Optional brain imaging and brain activity scans may be performed. Researchers measure changes in depression severity using the Montgomery-Asberg Depression Rating Scale MADRS and other mood and anxiety scales. Safety is monitored through adverse event reports, vital signs, laboratory tests, and electrocardiograms. The total participation spans the infusion sessions and follow-up assessments up to day 12 after each test session.

Researchers are studying mood disorders including depression, bipolar disorder, and suicide risk to better understand how these conditions affect individuals and their response to treatment. The study focuses on people aged 18 and older who are receiving treatment for these conditions and were also enrolled in a previous protocol. The goal is to identify factors that predict how patients respond to antidepressant treatments and to understand changes in suicidal thoughts. Participants will undergo personalized treatments for their mood disorders and receive standard clinical care that may be adjusted based on their needs. The study involves weekly interviews and questionnaires during treatment, with optional psychological tests, blood draws, sleep studies, and brain imaging performed at the beginning and end of participation. The study typically lasts up to 12 weeks but can be longer if treatment continues. During the study, participants will be regularly assessed using clinical rating scales such as the Montgomery Asberg Depression Rating Scale and the Scale for Suicidal Ideation. Data collection includes both in-person and remote evaluations. Researchers will monitor treatment effects and collect biological data to find predictors and biomarkers of treatment response. The study is conducted at the NIH Clinical Center and aims to support future improvements in managing mood disorders.

Researchers are evaluating the use of nebulized ketamine as a treatment for adults with moderate to severe depression in an inpatient psychiatric setting. This double-blind, randomized clinical trial compares nebulized ketamine with an active placebo, midazolam, to assess their effects on depressive symptoms. The study is designed to provide insights on whether inhaled ketamine can reduce depression when added to current medications and therapies. Participants will be randomly assigned to receive either nebulized ketamine at a dose calculated by body weight 1.5 mgkg or nebulized midazolam as an active comparator 0.03 mgkg. The study involves 4 to 5 visits depending on the treatment group, with dosing days requiring in-person attendance and monitoring for at least two hours. All other visits can be conducted remotely. Vital signs will be regularly collected during the observation period following dosing. Adults aged 18 and older diagnosed with moderate to severe major depressive disorder will be screened and enrolled. Throughout the 8 to 10 day study period, researchers will measure changes in depression using the Montgomery-sberg Depression Rating Scale MADRS and other scales assessing suicide ideation, dissociative effects, sedation, and agitation. Safety monitoring includes vital signs and side effect assessments. The study aims to capture both immediate and short-term effects of the treatments on depressive symptoms.