Experience-dependent information routing through the basolateral amygdala shapes behavioral outcomes.

It is well established that the basolateral amygdala (BLA) is an emotional processing hub that governs a diverse repertoire of behaviors. Selective engagement of a heterogeneous cell population in the BLA is thought to contribute to this flexibility in behavioral outcomes. However, whether this process is impacted by previous experiences that influence emotional processing remains unclear. Here we demonstrate that previous positive (enriched environment [EE]) or negative (chronic unpredictable stress [CUS]) experiences differentially influence the activity of populations of BLA principal neurons projecting to either the nucleus accumbens core or bed nucleus of the stria terminalis. Chemogenetic manipulation of these projection-specific neurons can mimic or occlude the effects of CUS and EE on behavioral outcomes to bidirectionally control avoidance behaviors and stress-induced helplessness. These data demonstrate that previous experiences influence the responsiveness of projection-specific BLA principal neurons, biasing information routing through the BLA, to drive divergent behavioral outcomes.

Changes in taste palatability across the estrous cycle are modulated by hypothalamic estradiol signaling.

Food intake varies across the stages of a rat's estrous cycle. It is reasonable to hypothesize that this cyclic fluctuation in consumption reflects an impact of hormones on taste palatability/preference, but evidence for this hypothesis has been mixed, and critical within-subject experiments in which rats sample multiple tastes during each of the four main estrous phases (metestrus, diestrus, proestrus, and estrus) have been scarce. Here, we assayed licking for pleasant (sucrose, NaCl, saccharin) and aversive (quinine-HCl, citric acid) tastes each day for 5-10 days while tracking rats' estrous cycles through vaginal cytology. Initial analyses confirmed the previously-described increased consumption of pleasant stimuli 24-48 hours following the time of high estradiol. A closer look, however, revealed this effect to reflect a general magnification of palatability-higher than normal preferences for pleasant tastes and lower than normal preferences for aversive tastes-during metestrus. We hypothesized that this phenomenon might be related to estradiol processing in the lateral hypothalamus (LH), and tested this hypothesis by inhibiting LH estrogen receptor activity with ICI 182,780 during tasting. Control infusions replicated the metestrus magnification of palatability pattern; ICI infusions blocked this effect as predicted, but failed to render preferences "cycle free," instead delaying the palatability magnification until diestrus. Clearly, estrous phase mediates details of taste palatability in a manner involving hypothalamic actions of estradiol; further work will be needed to explain the lack of a flat response across the cycle with hypothalamic estradiol binding inhibited, a result which perhaps suggests dynamic interplay between brain regions or hormones. Significance Statement: Consummatory behaviors are impacted by many variables, including naturally circulating hormones. While it is clear that consumption is particularly high during the stages following the high-estradiol stage of the rodent's estrous (and human menstrual) cycle, it is as of yet unclear whether this phenomenon reflects cycle stage-specific palatability (i.e., whether pleasant tastes are particularly delicious, and aversive tastes particularly disgusting, at particular phases). Here we show that palatability is indeed modulated by estrous phase, and that this effect is governed, at least in part, by the action of estradiol within the lateral hypothalamus. These findings shed light on the mechanisms underlying the adverse impact on human welfare due to irregularities observed across the otherwise cyclic menstrual process.

Early life stress impairs VTA coordination of BLA network and behavioral states.

Motivated behaviors, such as social interactions, are governed by the interplay between mesocorticolimbic structures, such as the ventral tegmental area (VTA), basolateral amygdala (BLA), and medial prefrontal cortex (mPFC). Adverse childhood experiences and early life stress (ELS) can impact these networks and behaviors, which is associated with increased risk for psychiatric illnesses. While it is known that the VTA projects to both the BLA and mPFC, the influence of these inputs on local network activity which govern behavioral states - and whether ELS impacts VTA-mediated network communication - remains unknown. Our study demonstrates that VTA inputs influence BLA oscillations and mPFC activity, and that ELS weakens the ability of the VTA to coordinate BLA network states, likely due to ELS-induced impairments in dopamine signaling between the VTA and BLA. Consequently, ELS mice exhibit increased social avoidance, which can be recapitulated in control mice by inhibiting VTA-BLA communication. These data suggest that ELS impacts social reward via the VTA-BLA dopamine network.

LiCl-induced sickness modulates rat gustatory cortical responses.

Gustatory cortex (GC), a structure deeply involved in the making of consumption decisions, presumably performs this function by integrating information about taste, experiences, and internal states related to the animal's health, such as illness. Here, we investigated this assertion, examining whether illness is represented in GC activity, and how this representation impacts taste responses and behavior. We recorded GC single-neuron activity and local field potentials (LFPs) from healthy rats and rats made ill (via LiCl injection). We show (consistent with the extant literature) that the onset of illness-related behaviors arises contemporaneously with alterations in 7 to 12 Hz LFP power at approximately 12 min following injection. This process was accompanied by reductions in single-neuron taste response magnitudes and discriminability, and with enhancements in palatability-relatedness-a result reflecting the collapse of responses toward a simple "good-bad" code visible in the entire sample, but focused on a specific subset of GC neurons. Overall, our data show that a state (illness) that profoundly reduces consumption changes basic properties of the sensory cortical response to tastes, in a manner that can easily explain illness' impact on consumption.

The function of groups of neurons changes from moment to moment.

Modern techniques that enable identification and targeted manipulation of neuron groups are frequently used to bolster theories that attribute specific behavioral functions to specific neuron types. These same techniques can also be used, however, to highlight limitations of such attribution, and to develop the argument that the question "what is the function of these neurons?" is ill-posed in the absence of temporal and network constraints. Here we do this, first reviewing evidence that neural responses are dynamic at multiple time scales, making the point that such changes in firing rates imply changes in what the neuron is doing. Studies involving brief perturbations of neural populations confirm this point, showing that the functions in which these populations participate change across seconds and even milliseconds. Based on these studies, we suggest that it is inappropriate to assign function to sets of neurons without contextualizing that assignment to specific times and network conditions.

Behavioral and Neurophysiological Signatures of Benzodiazepine-Related Driving Impairments.

Impaired driving due to drug use is a growing problem worldwide; estimates show that 18-23.5% of fatal accidents, and up to 34% of injury accidents may be caused by drivers under the influence of drugs (Drummer et al., 2003; Walsh et al., 2004; NHTSA, 2010). Furthermore, at any given time, up to 16% of drivers may be using drugs that can impair one's driving abilities (NHTSA, 2009). Currently, drug recognition experts (DREs; law enforcement officers with specialized training to identify drugged driving), have the most difficult time with identifying drivers potentially impaired on central nervous system (CNS) depressants (Smith et al., 2002). The fact that the use of benzodiazepines, a type of CNS depressant, is also associated with the greatest likelihood of causing accidents (Dassanayake et al., 2011), further emphasizes the need to improve research tools in this area which can facilitate the refinement of, or additions to, current assessments of impaired driving. Our laboratories collaborated to evaluate both the behavioral and neurophysiological effects of a benzodiazepine, alprazolam, in a driving simulation (miniSim(TM)). This drive was combined with a neurocognitive assessment utilizing time synched neurophysiology (electroencephalography, ECG). While the behavioral effects of benzodiazepines are well characterized (Rapoport et al., 2009), we hypothesized that, with the addition of real-time neurophysiology and the utilization of simulation and neurocognitive assessment, we could find objective assessments of drug impairment that could improve the detection capabilities of DREs. Our analyses revealed that (1) specific driving conditions were significantly more difficult for benzodiazepine impaired drivers and (2) the neurocognitive tasks' metrics were able to classify "impaired" vs. "unimpaired" with up to 80% accuracy based on lane position deviation and lane departures. While this work requires replication in larger studies, our results not only identified criteria that could potentially improve the identification of benzodiazepine intoxication by DREs, but also demonstrated the promise for future studies using this approach to improve upon current, real-world assessments of impaired driving.

Characterizing donation behavior from psychophysiological indices of narrative experience.

Research on narrative persuasion has yet to investigate whether this process influences behavior. The current study explored whether: (1) a narrative could persuade participants to donate to a charity, a prosocial, behavioral decision; (2) psychophysiological metrics can delineate the differences between donation/non-donation behaviors; and (3) donation behavior can be correlated with measures of psychophysiology, self-reported reactions to the narrative, and intrinsic characteristics. Participants (n = 49) completed personality/disposition questionnaires, viewed one of two versions of a narrative while EEG and ECG were recorded, completed a questionnaire regarding their reactions to the narrative, and were given an opportunity to donate to a charity related to the themes of the narrative. Results showed that: (1) 34.7% of participants donated; (2) psychophysiological metrics successfully delineated between donation behaviors and the effects of narrative version; and (3) psychophysiology and reactions to the narrative were better able to explain the variance (88 and 65%, respectively) in the amount donated than all 3 metrics combined as well as any metric alone. These findings demonstrate the promise of narrative persuasion for influencing prosocial, behavioral decisions. Our results also illustrate the utility of the previously stated metrics for understanding and possibly even manipulating behaviors resulting from narrative persuasion.

Identifying psychophysiological indices of expert vs. novice performance in deadly force judgment and decision making.

OBJECTIVE: To demonstrate that psychophysiology may have applications for objective assessment of expertise development in deadly force judgment and decision making (DFJDM). BACKGROUND: Modern training techniques focus on improving decision-making skills with participative assessment between trainees and subject matter experts primarily through subjective observation. OBJECTIVE metrics need to be developed. The current proof of concept study explored the potential for psychophysiological metrics in deadly force judgment contexts. METHOD: Twenty-four participants (novice, expert) were recruited. All wore a wireless Electroencephalography (EEG) device to collect psychophysiological data during high-fidelity simulated deadly force judgment and decision-making simulations using a modified Glock firearm. Participants were exposed to 27 video scenarios, one-third of which would have justified use of deadly force. Pass/fail was determined by whether the participant used deadly force appropriately. RESULTS: Experts had a significantly higher pass rate compared to novices (p < 0.05). Multiple metrics were shown to distinguish novices from experts. Hierarchical regression analyses indicate that psychophysiological variables are able to explain 72% of the variability in expert performance, but only 37% in novices. Discriminant function analysis (DFA) using psychophysiological metrics was able to discern between experts and novices with 72.6% accuracy. CONCLUSION: While limited due to small sample size, the results suggest that psychophysiology may be developed for use as an objective measure of expertise in DFDJM. Specifically, discriminant function measures may have the potential to objectively identify expert skill acquisition. APPLICATION: Psychophysiological metrics may create a performance model with the potential to optimize simulator-based DFJDM training. These performance models could be used for trainee feedback, and/or by the instructor to assess performance objectively.