Latent goal models for dynamic strategic interaction.

Understanding the principles by which agents interact with both complex environments and each other is a key goal of decision neuroscience. However, most previous studies have used experimental paradigms in which choices are discrete (and few), play is static, and optimal solutions are known. Yet in natural environments, interactions between agents typically involve continuous action spaces, ongoing dynamics, and no known optimal solution. Here, we seek to bridge this divide by using a "penalty shot" task in which pairs of monkeys competed against each other in a competitive, real-time video game. We modeled monkeys' strategies as driven by stochastically evolving goals, onscreen positions that served as set points for a control model that produced observed joystick movements. We fit this goal-based dynamical system model using approximate Bayesian inference methods, using neural networks to parameterize players' goals as a dynamic mixture of Gaussian components. Our model is conceptually simple, constructed of interpretable components, and capable of generating synthetic data that capture the complexity of real player dynamics. We further characterized players' strategies using the number of change points on each trial. We found that this complexity varied more across sessions than within sessions, and that more complex strategies benefited offensive players but not defensive players. Together, our experimental paradigm and model offer a powerful combination of tools for the study of realistic social dynamics in the laboratory setting.

Specific neural substrate linking respiration to locomotion.

When animals move, respiration increases to adapt for increased energy demands; the underlying mechanisms are still not understood. We investigated the neural substrates underlying the respiratory changes in relation to movement in lampreys. We showed that respiration increases following stimulation of the mesencephalic locomotor region (MLR) in an in vitro isolated preparation, an effect that persists in the absence of the spinal cord and caudal brainstem. By using electrophysiological and anatomical techniques, including whole-cell patch recordings, we identified a subset of neurons located in the dorsal MLR that send direct inputs to neurons in the respiratory generator. In semi-intact preparations, blockade of this region with 6-cyano-7-nitroquinoxaline-2,3-dione and (2R)-amino-5-phosphonovaleric acid greatly reduced the respiratory increases without affecting the locomotor movements. These results show that neurons in the respiratory generator receive direct glutamatergic connections from the MLR and that a subpopulation of MLR neurons plays a key role in the respiratory changes linked to movement.

Brain games: toward a neuroecology of social behavior.

In the target article, Schilbach et al. defend a "second-person neuroscience" perspective that focuses on the neural basis of social cognition during live, ongoing interactions between individuals. We argue that a second-person neuroscience would benefit from formal approaches borrowed from economics and behavioral ecology and that it should be extended to social interactions in nonhuman animals.

Initiation of locomotion in lampreys.

The spinal circuitry underlying the generation of basic locomotor synergies has been described in substantial detail in lampreys and the cellular mechanisms have been identified. The initiation of locomotion, on the other hand, relies on supraspinal networks and the cellular mechanisms involved are only beginning to be understood. This review examines some of the findings relative to the neural mechanisms involved in the initiation of locomotion of lampreys. Locomotion can be elicited by sensory stimulation or by internal cues associated with fundamental needs of the animal such as food seeking, exploration, and mating. We have described mechanisms by which escape swimming is elicited in lampreys in response to mechanical skin stimulation. A rather simple neural connectivity is involved, including sensory and relay neurons, as well as the brainstem rhombencephalic reticulospinal cells, which act as command neurons. We have shown that reticulospinal cells have intrinsic membrane properties that allow them to transform a short duration sensory input into a long-lasting excitatory command that activates the spinal locomotor networks. These mechanisms constitute an important feature for the activation of escape swimming. Other sensory inputs can also elicit locomotion in lampreys. For instance, we have recently shown that olfactory signals evoke sustained depolarizations in reticulospinal neurons and chemical activation of the olfactory bulbs with local injections of glutamate induces fictive locomotion. The mechanisms by which internal cues initiate locomotion are less understood. Our research has focused on one particular locomotor center in the brainstem, the mesencephalic locomotor region (MLR). The MLR is believed to channel inputs from many brain regions to generate goal-directed locomotion. It activates reticulospinal cells to elicit locomotor output in a graded fashion contrary to escape locomotor bouts, which are all-or-none. MLR inputs to reticulospinal cells use both glutamatergic and cholinergic transmission; nicotinic receptors on reticulospinal cells are involved. MLR excitatory inputs to reticulospinal cells in the middle (MRRN) are larger than those in the posterior rhombencephalic reticular nucleus (PRRN). Moreover at low stimulation strength, reticulospinal cells in the MRRN are activated first, whereas those in the PRRN require stronger stimulation strengths. The output from the MLR on one side activates reticulospinal neurons on both sides in a highly symmetrical fashion. This could account for the symmetrical bilateral locomotor output evoked during unilateral stimulation of the MLR in all animal species tested to date. Interestingly, muscarinic receptor activation reduces sensory inputs to reticulospinal neurons and, under natural conditions, the activation of MLR cholinergic neurons will likely reduce sensory inflow. Moreover, exposing the brainstem to muscarinic agonists generates sustained recurring depolarizations in reticulospinal neurons through pre-reticular effects. Cells in the caudal half of the rhombencephalon appear to be involved and we propose that the activation of these muscarinoceptive cells could provide additional excitation to reticulospinal cells when the MLR is activated under natural conditions. One important question relates to sources of inputs to the MLR. We found that substance P excites the MLR, whereas GABA inputs tonically maintain the MLR inhibited and removal of this inhibition initiates locomotion. Other locomotor centers exist such as a region in the ventral thalamus projecting directly to reticulospinal cells. This region, referred to as the diencephalic locomotor region, receives inputs from several areas in the forebrain and is likely important for goal-directed locomotion. In summary, this review focuses on the most recent findings relative to initiation of lamprey locomotion in response to sensory and internal cues in lampreys.

Clinical Impact of Pharmacogenetic-Guided Treatment for Patients Exhibiting Neuropsychiatric Disorders: A Randomized Controlled Trial.

Objective: Pharmacogenetic testing holds promise as a personalized medicine tool by permitting individualization of pharmacotherapy in accordance with genes influencing therapeutic response, side effects, and adverse events. The authors evaluated the effect on outcomes for patients diagnosed with neuropsychiatric disorders of pharmacogenetics (PGx)-guided treatment compared to usual standard of care. Methods: This was a prospective, randomized study of 237 patients at an outpatient community-based psychiatric practice conducted between April 2015 and October 2015. Baseline patient assessments and a buccal swab were collected for pharmacogenetic testing at study initiation. For the experimental group, PGx results were provided to the clinicians as guides to treatment. Control subjects were treated according to the usual standard of care with no clinician reference to their PGx results. Neuropsychiatric Questionnaire (NPQ) and Symbol Digit Coding Test (SDC) scores and adverse drug events, hospitalizations, and medication information were collected at 30, 60, and 90 days. Results: More than half (53%) of patients in the control group reported at least 1 adverse drug event compared to 28% of patients with PGx-guided medication management (P = .001). NPQ and SDC scores improved for both groups, but no statistical difference in efficacy as measured by these assessments was observed within the 90-day observation period. Conclusions: Pharmacogenetic testing may facilitate psychiatric drug therapy with greater tolerability and similar efficacy compared to standard of care. Trial Registration: ClinicalTrials.gov Identifier: NCT02411123​​.

A Specific Population of Reticulospinal Neurons Controls the Termination of Locomotion.

Locomotion requires the proper sequencing of neural activity to start, maintain, and stop it. Recently, brainstem neurons were shown to specifically stop locomotion in mammals. However, the cellular properties of these neurons and their activity during locomotion are still unknown. Here, we took advantage of the lamprey model to characterize the activity of a cell population that we now show to be involved in stopping locomotion. We find that these neurons display a burst of spikes that coincides with the end of swimming activity. Their pharmacological activation ends ongoing swimming, whereas the inactivation of these neurons dramatically impairs the rapid termination of swimming. These neurons are henceforth referred to as stop cells, because they play a crucial role in the termination of locomotion. Our findings contribute to the fundamental understanding of motor control and provide important details about the cellular mechanisms involved in locomotor termination.

The neuroethology of friendship.

Friendship pervades the human social landscape. These bonds are so important that disrupting them leads to health problems, and difficulties forming or maintaining friendships attend neuropsychiatric disorders like autism and depression. Other animals also have friends, suggesting that friendship is not solely a human invention but is instead an evolved trait. A neuroethological approach applies behavioral, neurobiological, and molecular techniques to explain friendship with reference to its underlying mechanisms, development, evolutionary origins, and biological function. Recent studies implicate a shared suite of neural circuits and neuromodulatory pathways in the formation, maintenance, and manipulation of friendships across humans and other animals. Health consequences and reproductive advantages in mammals additionally suggest that friendship has adaptive benefits. We argue that understanding the neuroethology of friendship in humans and other animals brings us closer to knowing fully what it means to be human.

Social learning in humans and other animals.

Decisions made by individuals can be influenced by what others think and do. Social learning includes a wide array of behaviors such as imitation, observational learning of novel foraging techniques, peer or parental influences on individual preferences, as well as outright teaching. These processes are believed to underlie an important part of cultural variation among human populations and may also explain intraspecific variation in behavior between geographically distinct populations of animals. Recent neurobiological studies have begun to uncover the neural basis of social learning. Here we review experimental evidence from the past few decades showing that social learning is a widespread set of skills present in multiple animal species. In mammals, the temporoparietal junction, the dorsomedial, and dorsolateral prefrontal cortex, as well as the anterior cingulate gyrus, appear to play critical roles in social learning. Birds, fish, and insects also learn from others, but the underlying neural mechanisms remain poorly understood. We discuss the evolutionary implications of these findings and highlight the importance of emerging animal models that permit precise modification of neural circuit function for elucidating the neural basis of social learning.

Neuronal reference frames for social decisions in primate frontal cortex.

Social decisions are crucial for the success of individuals and the groups that they comprise. Group members respond vicariously to benefits obtained by others, and impairments in this capacity contribute to neuropsychiatric disorders such as autism and sociopathy. We examined the manner in which neurons in three frontal cortical areas encoded the outcomes of social decisions as monkeys performed a reward-allocation task. Neurons in the orbitofrontal cortex (OFC) predominantly encoded rewards that were delivered to oneself. Neurons in the anterior cingulate gyrus (ACCg) encoded reward allocations to the other monkey, to oneself or to both. Neurons in the anterior cingulate sulcus (ACCs) signaled reward allocations to the other monkey or to no one. In this network of received (OFC) and foregone (ACCs) reward signaling, ACCg emerged as an important nexus for the computation of shared experience and social reward. Individual and species-specific variations in social decision-making might result from the relative activation and influence of these areas.

Bilateral connectivity in the brainstem respiratory networks of lampreys.

This study examines the connectivity in the neural networks controlling respiration in the lampreys, a basal vertebrate. Previous studies have shown that the lamprey paratrigeminal respiratory group (pTRG) plays a crucial role in the generation of respiration. By using a combination of anatomical and physiological techniques, we characterized the bilateral connections between the pTRGs and descending projections to the motoneurons. Tracers were injected in the respiratory motoneuron pools to identify pre-motor respiratory interneurons. Retrogradely labeled cell bodies were found in the pTRG on both sides. Whole-cell recordings of the retrogradely labeled pTRG neurons showed rhythmical excitatory currents in tune with respiratory motoneuron activity. This confirmed that they were related to respiration. Intracellular labeling of individual pTRG neurons revealed axonal branches to the contralateral pTRG and bilateral projections to the respiratory motoneuronal columns. Stimulation of the pTRG induced excitatory postsynaptic potentials in ipsi- and contralateral respiratory motoneurons as well as in contralateral pTRG neurons. A lidocaine HCl (Xylocaine) injection on the midline at the rostrocaudal level of the pTRG diminished the contralateral motoneuronal EPSPs as well as a local injection of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and (2R)-amino-5-phosphonovaleric acid (AP-5) on the recorded respiratory motoneuron. Our data show that neurons in the pTRG send two sets of axonal projections: one to the contralateral pTRG and another to activate respiratory motoneurons on both sides through glutamatergic synapses.

The interactions between locomotion and respiration.

Respiration is a vital motor activity requiring fine-tuning to adjust to metabolic changes. For instance, respiration increases in association with exercise. In this chapter, we review the mechanisms underlying respiratory changes during exercise. Three specific hypotheses were proposed. First, the chemoreception hypothesis suggests that chemoreceptors located centrally or peripherally modify breathing by detecting metabolic changes in arterial blood or cerebrospinal fluid. Second, the central command hypothesis stipulates that central neural connections from brain motor areas activate the respiratory centers during exercise. Third, the neural feedback hypothesis stipulates that sensory inputs from the contracting limb muscles modulate the respiratory centers during exercise. We present evidence from the literature supporting possible contributions from these three mechanisms. This review also addresses future research challenges relative to respiratory modulation during exercise.