Neural Basis of Decision-Making Deficits in Traumatic Brain Injury

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).

- 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