Neural Basis of Decision-Making Deficits in Traumatic Brain Injury

Study Description:

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.

Objectives:

• Quantify differences in performance on a decision-making task between TBI patients and healthy volunteers;
• Determine whether baseline features of mesocorticolimbic network structure and function predict subsequent decision-making performance in both TBI patients and healthy volunteers; and
• 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.

Endpoints:

Primary Endpoint: The primary outcome measure for both Experiment 1 and 2 is performance in a computerized decision-making task.

Secondary Endpoints: Secondary outcome measures will include quantitative estimates of structural and functional mesocorticolimbic network features, including MRI-based structural and functional connectivity, MEG-based functional connectivity, 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 features and decision-making task performance within a unified state-space framework (Experiment 1), as well as the ability of these network features to predict inter-individual differences in the effects of tDCS on decision-making task performance (Experiment 2).

• INCLUSION CRITERIA

Inclusion criteria

for Healthy Volunteers:

• Age 18 to 60
• Able to give consent
• Must be able to follow instructions and perform required tasks
• Absence of clinically significant abnormalities during neurological examination

Inclusion criteria

for TBI:

• Age 18 to 60
• Able to give consent
• Must be able to follow instructions and perform required tasks.
• 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 a healthcare provider 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 participants with childbearing capacity, 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