Learning theory suggests that animals attend to pertinent environmental cues when reward contingencies unexpectedly change so that learning can occur. We have previously shown that activity in basolateral nucleus of amygdala (ABL) responds to unexpected changes in reward value, consistent with unsigned prediction error signals theorized by Pearce and Hall. However, changes in activity were only present at the time of unexpected reward delivery, not during the time when the animal needed to attend to conditioned stimuli that would come to predict the reward. This suggested that a different brain area must be signaling the need for attention necessary for learning. One likely candidate to fulfill this role is the anterior cingulate cortex (ACC). To test this hypothesis, we recorded from single neurons in ACC as they performed the same behavioral task that we have used to dissociate signed from unsigned prediction errors in dopamine and ABL neurons. In this task rats chose between two fluid wells that produced varying magnitudes of and delays to reward. Consistent with previous work, we found that ACC detected errors of commission and reward prediction errors. We also found that activity during cue sampling encoded reward size, but not expected delay to reward. Finally, activity in ACC was elevated during trials in which attention was increased following unexpected up- and down-shifts in value. We conclude that ACC not only signals errors in reward prediction as previously reported, but also signals the need for enhanced neural resources during learning on trials subsequent to those errors.

Orbitofrontal cortex (OFC) lesions produce deficits in response inhibition and imaging studies suggest that activity in OFC is stronger on trials that require suppression of behavior, yet few studies have examined neural correlates at the single-unit level in a behavioral task that probes response inhibition without varying other factors, such as anticipated outcomes. Here we recorded from single neurons in lateral OFC in a task that required animals in the minority of trials to STOP or inhibit an ongoing movement and respond in the opposite direction. We found that population and single-unit firing was modulated primarily by response direction and movement speed, and that very few OFC neurons exhibited a response independent inhibition signal. Remarkably, the strength of the directional signal was not diminished on STOP trials and was actually stronger on STOP trials during conflict adaptation. Finally, directional signals were stronger during sessions in which rats had the most difficulty inhibiting behavior. These results suggest that "inhibition" deficits observed with OFC interference studies reflect deficits unrelated to signaling the need to inhibit behavior, but instead support a role for OFC in executive functions related to dissociating between two perceptually similar actions during response conflict.

The ability to inhibit action is critical for everyday behavior and is affected by a variety of disorders. Behavioral control and response inhibition is thought to depend on a neural circuit that includes the dorsal striatum, yet the neural signals that lead to response inhibition and its failure are unclear. To address this issue, we recorded from neurons in rat dorsomedial striatum (mDS) in a novel task in which rats responded to a spatial cue that signaled that reward would be delivered either to the left or to the right. On 80% of trials rats were instructed to respond in the direction cued by the light (GO). On 20% of trials a second light illuminated instructing the rat to refrain from making the cued movement and move in the opposite direction (STOP). Many neurons in mDS encoded direction, firing more or less strongly for GO movements made ipsilateral or contralateral to the recording electrode. Neurons that fired more strongly for contralateral GO responses were more active when rats were faster, showed reduced activity on STOP trials, and miscoded direction on errors, suggesting that when these neurons were overly active, response inhibition failed. Neurons that decreased firing for contralateral movement were excited during trials in which the rat was required to stop the ipsilateral movement. For these neurons activity was reduced when errors were made and was negatively correlated with movement time suggesting that when these neurons were less active on STOP trials, response inhibition failed. Finally, the activity of a significant number of neurons represented a global inhibitory signal, firing more strongly during response inhibition regardless of response direction. Breakdown by cell type suggests that putative medium spiny neurons (MSNs) tended to fire more strongly under STOP trials, whereas putative interneurons exhibited both activity patterns.

Traumatic brain injury (TBI) is a well-known consequence of participation in activities such as military combat or collision sports. But the wide variability in eliciting circumstances and injury severities makes the study of TBI as a uniform disease state impossible. Military Service members are under additional, unique threats such as exposure to explosive blast and its unique effects on the body. This review is aimed toward TBI researchers, as it covers important concepts and considerations for studying blast-induced head trauma. These include the comparability of blast-induced head trauma to other mechanisms of TBI, whether blast overpressure induces measureable biomarkers, and whether a biodosimeter can link blast exposure to health outcomes, using acute radiation exposure as a corollary. This examination is contextualized by the understanding of concussive events and their psychological effects throughout the past century’s wars, as well as the variables that predict sustaining a TBI and those that precipitate or exacerbate psychological conditions. Disclaimer: The views expressed in this article are solely the views of the authors and not those of the Department of Defense Blast Injury Research Coordinating Office, US Army Medical Research and Development Command, US Army Futures Command, US Army, or the Department of Defense.