Environmental enrichment (EE) emerged as a robust independent variable capable of influencing behavioral outcome in experimental studies after the fortuitous observation by renowned neuropsychologist Donald O. Hebb that rats raised as pets in his home performed markedly better on problem-solving tasks than those kept in the laboratory. In the subsequent years, numerous studies ensued demonstrating that EE was also capable of inducing neuroplasticity in normal (i.e., noninjured) rats. These behavioral and neural alterations provided the impetus for investigating EE as a potential therapy for traumatic brain injury (TBI), which, over the past two decades, has resulted in several reports. Hence, the aim of this review is to integrate the findings and present the current state of EE as a viable neurorehabilitation strategy for TBI. Using the specific key term searches “traumatic brain injury” and “environmental enrichment” or “enriched environment,” 30 and 30 experimental TBI articles were identified by PubMed and Scopus, respectively. Of these, 27 articles were common to both search engines. An additional article was found on PubMed using the key terms “enriched environment” and “fluid percussion.” A review of the bibliographies in the 34 articles did not yield additional citations. The overwhelming consensus of the 34 publications is that EE benefits behavioral and histological outcome after brain injury produced by various models. Further, the enhancements are observed in male and female as well as adult and pediatric rats and mice. Taken together, these cumulative findings provide strong support for EE as a generalized and robust preclinical model of neurorehabilitation. However, to further enhance the model and to more accurately mimic the clinic, future studies should continue to evaluate EE during more rehabilitation-relevant conditions, such as delayed and shorter time periods, as well as in combination with other therapeutic approaches, as we have been doing for the past few years.

Anxiety is a debilitating symptom of most psychiatric disorders, including major depression, post-traumatic stress disorder, schizophrenia, and addiction. A detrimental aspect of anxiety is disruption of prefrontal cortex (PFC)-mediated executive functions, such as flexible decision making. Here we sought to understand how anxiety modulates PFC neuronal encoding of flexible shifting between behavioral strategies. We used a clinically substantiated anxiogenic treatment to induce sustained anxiety in rats and recorded from dorsomedial PFC (dmPFC) and orbitofrontal cortex (OFC) neurons while they were freely moving in a home cage and while they performed a PFC-dependent task that required flexible switches between rules in two distinct perceptual dimensions. Anxiety elicited a sustained background “hypofrontality” in dmPFC and OFC by reducing the firing rate of spontaneously active neuronal subpopulations. During task performance, the impact of anxiety was subtle, but, consistent with human data, behavior was selectively impaired when previously correct conditions were presented as conflicting choices. This impairment was associated with reduced recruitment of dmPFC neurons that selectively represented task rules at the time of action. OFC rule representation was not affected by anxiety. These data indicate that a neural substrate of the decision-making deficits in anxiety is diminished dmPFC neuronal encoding of task rules during conflict-related actions. Given the translational relevance of the model used here, the data provide a neuronal encoding mechanism for how anxiety biases decision making when the choice involves overcoming a conflict. They also demonstrate that PFC encoding of actions, as opposed to cues or outcome, is especially vulnerable to anxiety.SIGNIFICANCE STATEMENTA debilitating aspect of anxiety is its impact on decision making and flexible control of behavior. These cognitive constructs depend on proper functioning of the prefrontal cortex (PFC). Understanding how anxiety affects PFC encoding of cognitive events is of great clinical and evolutionary significance. Using a clinically valid experimental model, we find that, under anxiety, decision making may be skewed by salient and conflicting environmental stimuli at the expense of flexible top-down guided choices. We also find that anxiety suppresses spontaneous activity of PFC neurons, and weakens encoding of task rules by dorsomedial PFC neurons. These data provide a neuronal encoding scheme for how anxiety disengages PFC during decision making.