Exposure to uncertainty mediates the effects of traumatic brain injury on probabilistic decision-making in rats

ABSTRACT

Primary Objective: Traumatic brain injury (TBI) is associated with numerous psychiatric comorbidities, and subclinical psychiatric symptoms. While many symptoms have been replicated in animal models of brain injury, a vast majority of studies utilize naïve rats as subjects, which fail to mimic the complex learning history of human patients.

Methods and Procedures: In the current study, we evaluated the effects of a brain injury in animals with early exposure to uncertainty on post-injury decision-making in a probabilistic task, the rodent gambling task (RGT).

Main Outcomes and Results: Exposure to uncertainty resulted in a heterogeneous sample relative to prior publications, and brain-injured rats showed no deficits in choice behavior compared to shams which contrasts with large, pervasive deficits in previously published work. However, TBI increased impulsivity and caused transient changes in behavioral variables indicative of initial motivational deficits (pellets earned, omitted responses). Notably, effects of amphetamine were similar on this heterogeneous sample of rats relative to a number of other published reports, suggesting consistent effects of gross monoaminergic manipulations on choice behavior, independent of experience.

Conclusions: Going forward, translational studies need to consider the heterogeneity that exists at the clinical level and account for these problems when modeling diseases in animals.

KEYWORDS:

• Brain injury
• rodent gambling task
• impulsivity
• environment
• uncertainty

Author Disclosures

This work was supported by the Canadian Institutes for Health Research, the Michael Smith Foundation for Health Research, Southern Regional Education Board, and West Virginia University. The authors have no financial interest in the outcome of this research. CAW has served as a consultant for Shire pharmaceuticals in unrelated matters.

Data Availability

Data will be made available on request to the corresponding author.

Additional information

Funding

This work was supported by the Canadian Institutes for Health Research (Institute of Neurosciences, Mental Health and Addiction, PJT 148631), the Michael Smith Foundation for Health Research, Southern Regional Education Board, and West Virginia University.