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.


Objectives Deficits in decision-making are commonly found in individuals after traumatic brain injury (TBI) and can have a severe negative impact on quality of life. Converging evidence from both animal model and human studies suggest that decision-making deficits are linked with abnormal mesocorticolimbic network structure and function, and could potentially be mitigated through interventions that improve function within these neuronal circuits. The objectives of this protocol are to: (1) quantify differences in performance on a decision-making task between TBI patients and healthy volunteers; (2) determine whether baseline features of mesocorticolimbic network structure and function predict subsequent decision-making performance in both TBI patients and healthy volunteers; and (3) determine if facilitatory transcranial direct current stimulation (tDCS) applied over the dorsolateral prefrontal cortex (dlPFC), a mesocorticolimbic network region crucially involved in decision-making, improves decision-making after TBI. Study Population Up to 40 healthy adult volunteers and 40 TBI patients will be recruited under the protocol to participate in up to two experiments. Design We plan to accomplish the two objectives listed above within two experiments. Experiment 1 examines performance differences between TBI patients and healthy volunteers on a decision-making task, and explores whether baseline features of mesocorticolimbic network structure and function predict subsequent decision-making performance in TBI patients and healthy volunteers. Experiment 2, a proof-of-principle study, uses a sham-controlled, double-blind experimental design to examine whether facilitatory tDCS, a non-invasive intervention used recently to augment a range of cognitive functions, enhances decision-making performance in the same cohort of TBI patients and healthy volunteers. Outcome Measures The primary outcome measure for both Experiment 1 and 2 is performance in a computerized decision-making task. Secondary outcome measures will include quantitative estimates of structural and functional mesocorticolimbic network features, including MRI-based structural and functional connectivity, MEG-based functional dynamics, baseline dlPFC GABA concentration measured with magnetic resonance spectroscopy (MRS) imaging, dopamine D2 receptor binding potential within mesocorticolimbic subcortical nuclei measured with [11C]raclopride PET (Experiment 1). Multimodal data fusion modeling will be used to explore the predictive relationship between baseline mesocorticolimbic network states and decision-making task performance within a unified state-space framework (Experiment 1), as well as the ability of these network states to predict inter-individual differences in the effects of tDCS on decision-making task performance (Experiment 2).

Eligibility Criteria:

- INCLUSION CRITERIA - Age 18 to 60 - Able to give consent - Must be able to follow instructions and perform required tasks - For healthy volunteers, absence of clinically significant abnormalities during neurological examination Additional Inclusion Criteria for TBI: -History of having a sustained, traumatically induced (e.g., collision between the head and an object, or sudden acceleration/deceleration of the brain without direct external trauma to the head) physiological disruption of brain function, as manifested by at least one of the following (based on the American Congress of Rehabilitation Medicine Criteria): - Any period of loss of consciousness - Any loss of memory for events immediately before or after the accident - Focal neurological deficit(s) that may or may not be transient - Any alteration in mental state at the time of the accident (e.g., feeling dazed, disoriented, or confused) - Presentation to an Emergency Department within 24 hours of the injury event - History of self-reported complaints or clinical findings related to planning or decision-making deficits EXCLUSION CRITERIA - Pre-existing and disabling major psychiatric (e.g., schizophrenia, bipolar disorder or post-traumatic stress disorder) or neurological disease (e.g., stroke, dementia, epilepsy, or multiple sclerosis). - Present use of prescribed stimulants (e.g., methylphenidate or amphetamines) - Present use of prescribed dopamine agonists/antagonists other than amantadine - For female participants, pregnancy (for MRI and PET procedures) or nursing (for PET procedures only) - Contraindication to PET procedures (for PET procedures only) - Contraindication to MRI procedures as per MRI Center screening questionnaire (for MRI procedures only) - Inability to participate in at least two of the imaging procedures (PET, MRI or MEG) due to contraindications - Staff from our section - For TBI patients, history of a penetrating head wound - For healthy volunteers, history of any type of traumatically induced head injury resulting in presentation to an Emergency Department within 24 hours of the injury event

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