Behavioral Interventions Can Improve Brain Injury-Induced Deficits in Behavioral Flexibility and Impulsivity Linked to Impaired Reward-Feedback Beta Oscillations.

Traumatic brain injury (TBI) affects a large population, resulting in severe cognitive impairments. Although cognitive rehabilitation is an accepted treatment for some deficits, studies in patients are limited in ability to probe physiological and behavioral mechanisms. Therefore, animal models are needed to optimize strategies. Frontal TBI in a rat model results in robust and replicable cognitive deficits, making this an ideal candidate for investigating various behavioral interventions. In this study, we report three distinct frontal TBI experiments assessing behavior well into the chronic post-injury period using male Long-Evans rats. First, we evaluated the impact of frontal injury on local field potentials recorded simultaneously from 12 brain regions during a probabilistic reversal learning (PbR) task. Next, a set of rats were tested on a similar PbR task or an impulsivity task (differential reinforcement of low-rate behavior [DRL]) and half received salient cues associated with reinforcement contingencies to encourage engagement in the target behavior. After intervention on the PbR task, brains were stained for markers of activity. On the DRL task, cue relevance was decoupled from outcomes to determine if beneficial effects persisted on impulsive behavior. TBI decreased the ability to detect reinforced outcomes; this was evident in task performance and reward-feedback signals occurring at beta frequencies in lateral orbitofrontal cortex (OFC) and associated frontostriatal regions. The behavioral intervention improved flexibility and increased OFC activity. Intervention also reduced impulsivity, even after cues were decoupled, which was partially mediated by improvements in timing behavior. The current study established a platform to begin investigating cognitive rehabilitation in rats and identified a strong role for dysfunctional OFC signaling in probabilistic learning after frontal TBI.

Acute gut microbiome changes after traumatic brain injury are associated with chronic deficits in decision-making and impulsivity in male rats.

The mechanisms underlying chronic psychiatric-like impairments after traumatic brain injury (TBI) are currently unknown. The goal of the present study was to assess the role of diet and the gut microbiome in psychiatric symptoms after TBI. Rats were randomly assigned to receive a high-fat diet (HFD) or calorie-matched low-fat diet (LFD). After 2 weeks of free access, rats began training on the rodent gambling task (RGT), a measure of risky decision-making and motor impulsivity. After training, rats received a bilateral frontal TBI or a sham procedure and continued postinjury testing for 10 weeks. Fecal samples were collected before injury and 3-, 30-, and 60 days postinjury to evaluate the gut microbiome. HFD altered the microbiome, but ultimately had low-magnitude effects on behavior and did not modify functional outcomes after TBI. Injury-induced functional deficits were far more robust; TBI substantially decreased optimal choice and increased suboptimal choice and motor impulsivity on the RGT. TBI also affected the microbiome, and a model comparison approach revealed that bacterial diversity measured 3 days postinjury was predictive of chronic psychiatric-like deficits on the RGT. A functional metagenomic analysis identified changes to dopamine and serotonin synthesis pathways as a potential candidate mechanism. Thus, the gut may be a potential acute treatment target for psychiatric symptoms after TBI, as well as a biomarker for injury and deficit severity. However, further research will be needed to confirm and extend these findings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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

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.

Stimulus contributions to operant resurgence.

In two experiments, pigeons were exposed to a three-phase resurgence procedure (train Response A; extinguish Response A and train Response B; extinguish Response B). In the first experiment, the stimuli associated with phases were different, resulting in a resurgence procedure combined with an ABC renewal procedure. Presenting the novel stimulus, C, during extinction of both responses in the third phase resulted in minimal resurgence. Subsequently, substituting the original training Stimulus A for Stimulus C resulted in resurgence with all pigeons. In the second experiment, resurgence with the same stimuli present in all three phases of the resurgence procedure (AAA) was compared concurrently with a resurgence procedure in which the ABC renewal procedure used in Experiment 1 was superimposed. Substantially more resurgence occurred with the AAA procedure compared to the ABC procedure. Although ABC renewal in combination with the resurgence procedure generated some resurgence, such recurrent responding was attenuated relative to that observed when the stimulus conditions were constant across phases. Combined with earlier research showing the enhancing effects of combining resurgence and ABA renewal procedures, the present results elaborate on how stimuli correlated with certain behavioral histories affect the course of operant resurgence.