The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, is looking for individuals to participate in clinical studies. Participating in clinical trials allows you to play an active role in research on the nature and causes of many disorders of the brain and nervous system, and to possibly help physician-scientists develop future treatments. The information below is designed to help you quickly learn about actively recruiting research studies for which you or someone you know may be eligible.

Description:

- Males and females (n=30), between the ages of 18 and 55 years in the chronic stage after TBI who experience deficits in neuropsychological function from TBIs incurred 6 months after the injury, will be recruited from military treatment facilities or civilian clinics when presenting for clinical management of TBI or post-concussive symptoms. - 1. Study participants will be evaluated using brain MRI, psychometric measures adapted from the TBI Common Data Elements, attention tests and information about details of the injury and experience of post-concussive symptoms will be recorded. Transcranial magnetic stimulation (TMS) with placebo and with methylphenidate (60 mg by mouth) challenge will be performed to predict a stimulant response. - 2. Subjects will be studied with [11C]-raclopride PET in two imaging sessions. One session will be after administration of placebo and the other after methylphenidate, 60 mg by mouth. Both placebo and methylphenidate will be given 60 minutes prior to injection of [11C]-raclopride to allow for peak uptake of methylphenidate in the brain. The binding potential of [11C]-raclopride relative to a non-displaceable reference region (cerebellum), BPND, will be used as a measure of D2/D3 receptor availability. The difference in BPND between methylphenidate and placebo (ΔBPND) is used to measure of tonic DA release. - 3. Subjects will then be treated with oral methylphenidate, using a forced titration up to a dose of 30 mg given twice daily for 4 weeks. At that point, the neuropsychologic tests are repeated. - Outcome measures: The primary outcome is change in information processing speed during neuropsychologic testing.

Eligibility Criteria:

Inclusion Criteria: - Age 18 - 55 years, inclusive - A history of having sustained a moderate or severe TBI > 6 months prior to enrollment. Evidence will be any one of the following 3 criteria: 1. GCS 3 - 12 (GCS obtained in Emergency Room and noted in medical record) 2. Post-traumatic amnesia > 24 hours 3. TBI-related abnormality on neuroimaging (either CT or MRI). - Persistent post-concussive symptoms, according to the DSM-IV Research Criteria for Post-Concussional Disorder, including: 1. Difficulty in attention or memory. 2. One or more of the following symptoms, which started shortly after the trauma and persist for at least three months: 1. Fatigability 2. Disordered sleep 3. Changes in personality 4. Apathy or lack of spontaneity 3. Symptoms in criteria (a) and (b) must have their onset after trauma, or there was a significant worsening of pre-existing symptoms after trauma. 4. Disturbance from these symptoms causes significant impairment of social or occupational functioning and represents a significant decline from previous level of functioning. - Ability to read, write, and speak English - Ability to give informed consent. Exclusion Criteria: - Evidence of penetrating brain injury. - Contraindication to methylphenidate therapy: 1. Known glaucoma (consistently raised intraocular pressure with or without associated optic nerve damage) 2. Motor tics or a family history of Tourette's syndrome (diagnosed by presence of both multiple motor and one or more vocal tics over the period of a year, with no more than three consecutive tic-free months) 3. Known hypersensitivity to methylphenidate (hives, difficulty breathing, and swelling of face, lips, tongue, or throat). 4. Known severe anxiety or restlessness which prevents from doing day to day activities. 5. Known preexisting hypertension, heart failure, myocardial infarction, or ventricular arrhythmia. 6. Known preexisting psychosis, bipolar illness. 7. History of seizures, or interictal epileptiform discharges (IEDs) on EEG in absence of seizures. 8. Known peripheral vasculopathy, including Raynaud's phenomenon. 9. History of drug dependence or alcoholism. 10. Concomitant treatment with coumadin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and tricyclic drugs (e.g., imipramine, clomipramine, desipramine). 11. Concomitant therapy with monoamine oxidase inhibitors (such as Marplan (isocarboxazid), Nardil (phenelzine), Emsam (selegiline), and Parnate (tranylcypromine)) 12. Concomitant treatment with blood pressure medication (both for high and low blood pressure). 13. Pregnancy 14. Breastfeeding - History or evidence of disabling pre-existing or co-existing disabling neurologic or psychiatric disorders not related to TBI, such as: 1. Multiple sclerosis, pre- or co-existing 2. Stroke (other than stroke at the time of TBI) 3. Pre-existing disabling developmental disorder 4. Pre-existing epilepsy 5. Pre-existing major depressive disorder, aggressive behavior, hostility 6. Pre-existing schizophrenia - Contraindication to MRI scanning 1. Ferromagnetic metal in the cranial cavity or eye, e.g., aneurysm clip, implanted neural stimulator, cochlear implant, or ocular foreign body 2. Implanted cardiac pacemaker or auto-defibrillator or pump 3. Non-removable body piercing 4. Claustrophobia 5. Inability to lie supine for two hours - Contraindication to TMS, such as metal in the cranial cavity or implanted electronic hardware. - Current participation in other interventional clinical trial - Non-adherence to use of effective method of contraception for females of able to become pregnant for time from enrollment to the study until 2 weeks after completion of the study drug. - Present history of alcohol and substance abuse disorder determined by DSM-IV - Body mass index (BMI) > 30

Study Design:

Study Location:

Maryland