Knowing me, knowing you: Interpersonal similarity improves predictive accuracy and reduces attributions of harmful intent.

To benefit from social interactions, people need to predict how their social partners will behave. Such predictions arise through integrating prior expectations with evidence from observations, but where the priors come from and whether they influence the integration into beliefs about a social partner is not clear. Furthermore, this process can be affected by factors such as paranoia, in which the tendency to form biased impressions of others is common. Using a modified social value orientation (SVO) task in a large online sample (n = 697), we showed that participants used a Bayesian inference process to learn about partners, with priors that were based on their own preferences. Paranoia was associated with preferences for earning more than a partner and less flexible beliefs regarding a partner's social preferences. Alignment between the preferences of participants and their partners was associated with better predictions and with reduced attributions of harmful intent to partners. Together, our data and model expand upon theories of interpersonal relationships by demonstrating how dyadic similarity mechanistically influences social interaction by generating more accurate predictions and less threatening impressions.

Disrupted habenula function in major depression.

The habenula is a small, evolutionarily conserved brain structure that plays a central role in aversive processing and is hypothesised to be hyperactive in depression, contributing to the generation of symptoms such as anhedonia. However, habenula responses during aversive processing have yet to be reported in individuals with major depressive disorder (MDD). Unmedicated and currently depressed MDD patients (N=25, aged 18-52 years) and healthy volunteers (N=25, aged 19-52 years) completed a passive (Pavlovian) conditioning task with appetitive (monetary gain) and aversive (monetary loss and electric shock) outcomes during high-resolution functional magnetic resonance imaging; data were analysed using computational modelling. Arterial spin labelling was used to index resting-state perfusion and high-resolution anatomical images were used to assess habenula volume. In healthy volunteers, habenula activation increased as conditioned stimuli (CSs) became more strongly associated with electric shocks. This pattern was significantly different in MDD subjects, for whom habenula activation decreased significantly with increasing association between CSs and electric shocks. Individual differences in habenula volume were negatively associated with symptoms of anhedonia across both groups. MDD subjects exhibited abnormal negative task-related (phasic) habenula responses during primary aversive conditioning. The direction of this effect is opposite to that predicted by contemporary theoretical accounts of depression based on findings in animal models. We speculate that the negative habenula responses we observed may result in the loss of the capacity to actively avoid negative cues in MDD, which could lead to excessive negative focus.

The specificity of Pavlovian regulation is associated with recovery from depression.

BACKGROUND: Changes in reflexive emotional responses are hallmarks of depression, but how emotional reflexes make an impact on adaptive decision-making in depression has not been examined formally. Using a Pavlovian-instrumental transfer (PIT) task, we compared the influence of affectively valenced stimuli on decision-making in depression and generalized anxiety disorder compared with healthy controls; and related this to the longitudinal course of the illness. METHOD: A total of 40 subjects with a current DSM-IV-TR diagnosis of major depressive disorder, dysthymia, generalized anxiety disorder, or a combination thereof, and 40 matched healthy controls performed a PIT task that assesses how instrumental approach and withdrawal behaviours are influenced by appetitive and aversive Pavlovian conditioned stimuli (CSs). Patients were followed up after 4-6 months. Analyses focused on patients with depression alone (n = 25). RESULTS: In healthy controls, Pavlovian CSs exerted action-specific effects, with appetitive CSs boosting active approach and aversive CSs active withdrawal. This action-specificity was absent in currently depressed subjects. Greater action-specificity in patients was associated with better recovery over the follow-up period. CONCLUSIONS: Depression is associated with an abnormal influence of emotional reactions on decision-making in a way that may predict recovery.

Development, Evaluation and Implementation of Chief Complaint Groupings to Activate Data Collection: A Multi-Center Study of Clinical Decision Support for Children with Head Trauma.

BACKGROUND: Overuse of cranial computed tomography scans in children with blunt head trauma unnecessarily exposes them to radiation. The Pediatric Emergency Care Applied Research Network (PECARN) blunt head trauma prediction rules identify children who do not require a computed tomography scan. Electronic health record (EHR) based clinical decision support (CDS) may effectively implement these rules but must only be provided for appropriate patients in order to minimize excessive alerts. OBJECTIVES: To develop, implement and evaluate site-specific groupings of chief complaints (CC) that accurately identify children with head trauma, in order to activate data collection in an EHR. METHODS: As part of a 13 site clinical trial comparing cranial computed tomography use before and after implementation of CDS, four PECARN sites centrally developed and locally implemented CC groupings to trigger a clinical trial alert (CTA) to facilitate the completion of an emergency department head trauma data collection template. We tested and chose CC groupings to attain high sensitivity while maintaining at least moderate specificity. RESULTS: Due to variability in CCs available, identical groupings across sites were not possible. We noted substantial variability in the sensitivity and specificity of seemingly similar CC groupings between sites. The implemented CC groupings had sensitivities greater than 90% with specificities between 75-89%. During the trial, formal testing and provider feedback led to tailoring of the CC groupings at some sites. CONCLUSIONS: CC groupings can be successfully developed and implemented across multiple sites to accurately identify patients who should have a CTA triggered to facilitate EHR data collection. However, CC groupings will necessarily vary in order to attain high sensitivity and moderate-to-high specificity. In future trials, the balance between sensitivity and specificity should be considered based on the nature of the clinical condition, including prevalence and morbidity, in addition to the goals of the intervention being considered.

Memory, modelling and Marr: a commentary on Marr (1971) 'Simple memory: a theory of archicortex'.

David Marr's theory of the archicortex, a brain structure now more commonly known as the hippocampus and hippocampal formation, is an epochal contribution to theoretical neuroscience. Addressing the problem of how information about 10 000 events could be stored in the archicortex during the day so that they can be retrieved using partial information and then transferred to the neocortex overnight, the paper presages a whole wealth of later empirical and theoretical work, proving impressively prescient. Despite this impending success, Marr later apparently grew dissatisfied with this style of modelling, but he went on to make seminal suggestions that continue to resonate loudly throughout the field of theoretical neuroscience. We describe Marr's theory of the archicortex and his theory of theories, setting them into their original and a contemporary context, and assessing their impact. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

How receptor diffusion influences gradient sensing.

Chemotaxis, or directed motion in chemical gradients, is critical for various biological processes. Many eukaryotic cells perform spatial sensing, i.e. they detect gradients by comparing spatial differences in binding occupancy of chemosensory receptors across their membrane. In many theoretical models of spatial sensing, it is assumed, for the sake of simplicity, that the receptors concerned do not move. However, in reality, receptors undergo diverse modes of diffusion, and can traverse considerable distances in the time it takes such cells to turn in an external gradient. This sets a physical limit on the accuracy of spatial sensing, which we explore using a model in which receptors diffuse freely over the membrane. We find that the Fisher information carried in binding and unbinding events decreases monotonically with the diffusion constant of the receptors.

Disorders of compulsivity: a common bias towards learning habits.

Why do we repeat choices that we know are bad for us? Decision making is characterized by the parallel engagement of two distinct systems, goal-directed and habitual, thought to arise from two computational learning mechanisms, model-based and model-free. The habitual system is a candidate source of pathological fixedness. Using a decision task that measures the contribution to learning of either mechanism, we show a bias towards model-free (habit) acquisition in disorders involving both natural (binge eating) and artificial (methamphetamine) rewards, and obsessive-compulsive disorder. This favoring of model-free learning may underlie the repetitive behaviors that ultimately dominate in these disorders. Further, we show that the habit formation bias is associated with lower gray matter volumes in caudate and medial orbitofrontal cortex. Our findings suggest that the dysfunction in a common neurocomputational mechanism may underlie diverse disorders involving compulsion.

The influence of receptor positioning on chemotactic information.

Chemotaxis, or gradient following, is important in many biological systems, but suffers from noise. How receptors are positioned on the cell or sensing device influences the quality of the inferences they can support about the gradient, suggesting that their configuration might be optimised. We show that for an elliptical sensing device, inhomogeneous receptor placement could be a potential approach for cells to eliminate bias in the posterior distribution of the gradient direction. We use information theory to calculate the mutual information between the gradient and the binding pattern, thus finding the optimal receptor arrangement for gradient sensing.

Dopamine, reinforcement learning, and addiction.

Dopamine is intimately linked with the modes of action of drugs of addiction. However, although its role in the initiation of drug abuse seems relatively uncomplicated, its possible involvement in the development of compulsive drug taking, and indeed vulnerability and relapse, is less clear. We first describe a modern reinforcement learning view of affective control, focusing on the roles for dopamine. We then use this as a framework to sketch various notions of the neuromodulator's possible participation in initiation and compulsion. We end with some pointers towards future theoretical developments.

Acetylcholine contributes through muscarinic receptors to attentional modulation in V1.

Attention exerts a strong influence over neuronal processing in cortical areas. It selectively increases firing rates and affects tuning properties, including changing receptive field locations and sizes. Although these effects are well studied, their cellular mechanisms are poorly understood. To study the cellular mechanisms, we combined iontophoretic pharmacological analysis of cholinergic receptors with single cell recordings in V1 while rhesus macaque monkeys (Macaca mulatta) performed a task that demanded top-down spatial attention. Attending to the receptive field of the V1 neuron under study caused an increase in firing rates. Here we show that this attentional modulation was enhanced by low doses of acetylcholine. Furthermore, applying the muscarinic antagonist scopolamine reduced attentional modulation, whereas the nicotinic antagonist mecamylamine had no systematic effect. These results demonstrate that muscarinic cholinergic mechanisms play a central part in mediating the effects of attention in V1.

Putting the computation back into computational modeling.

Many different varieties of modeling coexist in theoretical neuroscience. Here, we consider the positive and negative implications, for theories of schizophrenia, of a crucial distinction between computational and mathematical modeling.

Test characteristics of the urine Gram stain in infants

OBJECTIVE: The utility of the Gram stain for the preliminary diagnosis of urinary tract infections (UTI) in infants or= 38.0 degrees C presenting to a pediatric emergency department during 2 consecutive winter seasons. Single pathogen growth of >or= 10(4) cfu/mL from a catheterized specimen and >or= 10(3) cfu/mL from a suprapubic specimen was considered positive. A positive Gram stain was defined as the identification of any organisms. Urinalysis was tested for the presence of nitrites and for leukocyte esterase (LE). Urine microscopy was analyzed for white blood cells per high power field (WBC/hpf). RESULTS: Fourteen of 246 patients were excluded; 11 because no Gram stain was completed. Of the remaining 232 patients, Gram stain had a sensitivity of 85.2% (95% CI 71.9-98.6%), a specificity of 99.0% (95% CI 97.7-100%), a likelihood ratio for a positive test of 87.3 (95% CI 21.8-349.9), and a likelihood ratio for a negative test of 0.15 (95% CI 0.06-0.37). There were 193 specimens for which a Gram stain and a complete UA and microscopy were completed and compared. Urine microscopy had a lower sensitivity and specificity than Gram stain for both >or= 5 WBC/hpf and >or= 10 WBC/hpf. In addition to the Gram stain, a dipstick negative for nitrites and LE had a low negative likelihood ratio (0.16), useful for decreasing the likelihood of a UTI. CONCLUSIONS: The Gram stain has excellent test characteristics for the preliminary diagnosis of a UTI in febrile infants. Patient disposition and therapy will likely change if clinical protocols and guidelines use the Gram stain rather than urine microscopy for preliminary diagnosis of UTI in infants.

Medical causes of pneumomediastinum in children.

The purpose of this study was to determine the possible causes, clinical findings, and associated complications of pneumomediastinum in children. Medical records from January 1985 to December 1994 were retrospectively reviewed at Children's Hospital Medical Center of Akron using International Classification of Diseases, ninth revision, codes to identify cases of pneumomediastinum. The medical causes, nontraumatic and noniatrogenic, of pneumomediastinum were studied; intubated or trauma patients and patients having undergone procedures were excluded. Neonates were also excluded. Twenty-nine cases of pneumomediastinum were identified. Two patients (7%) had recurrent pneumomediastinum. Only the first episode of pneumomediastinum was included in the data analysis. Twenty males (69%) and nine females (31%) were affected. The most common medical causes of pneumomediastinum were asthma exacerbations (17/59%) and infections (8/28%). Over the 10-year period, the prevalence of pneumomediastinum in children with asthma exacerbations was 0.2% (21/10,472); 1% (1/126) in children with airway foreign bodies and 0.2% (1/351) in children with esophageal foreign bodies. The most common signs and symptoms were subcutaneous emphysema (22/76%), sore throat or neck pain (11/38%), and Hamman's crunch (3/10%). The most common complication was pneumothorax with small pneumothoraces in 2 patients (7%) and a tension pneumothorax in 1 asthmatic with recurrent pneumomediastinum. Patients without sore throat or neck pain and patients admitted to the intensive care unit had greater hospital lengths of stay. Pneumomediastinum appears to be uncommon in children. The most common medical causes were asthma and infections. The most common signs and symptoms were subcutaneous emphysema, sore throat or neck pain, and Hamman's crunch. The most common complication was pneumothorax. The clinical significance of pneumomediastinum is its cause and association with significant complications.

Learning and selective attention.

Selective attention involves the differential processing of different stimuli, and has widespread psychological and neural consequences. Although computational modeling should offer a powerful way of linking observable phenomena at different levels, most work has focused on the relatively narrow issue of constraints on processing resources. By contrast, we consider statistical and informational aspects of selective attention, divorced from resource constraints, which are evident in animal conditioning experiments involving uncertain predictions and unreliable stimuli. Neuromodulatory systems and limbic structures are known to underlie attentional effects in such tasks.

The involvement of recurrent connections in area CA3 in establishing the properties of place fields: a model.

Strong constraints on the neural mechanisms underlying the formation of place fields in the rodent hippocampus come from the systematic changes in spatial activity patterns that are consequent on systematic environmental manipulations. We describe an attractor network model of area CA3 in which local, recurrent, excitatory, and inhibitory interactions generate appropriate place cell representations from location- and direction-specific activity in the entorhinal cortex. In the model, familiarity with the environment, as reflected by activity in neuromodulatory systems, influences the efficacy and plasticity of the recurrent and feedforward inputs to CA3. In unfamiliar, novel, environments, mossy fiber inputs impose activity patterns on CA3, and the recurrent collaterals and the perforant path inputs are subject to graded Hebbian plasticity. This sculpts CA3 attractors and associates them with activity patterns in the entorhinal cortex. In familiar environments, place fields are controlled by the way that perforant path inputs select among the attractors. Depending on the training experience provided, the model generates place fields that are either directional or nondirectional and whose changes when the environment undergoes simple geometric transformations are in accordance with experimental data. Representations of multiple environments can be stored and recalled with little interference, and these have the appropriate degrees of similarity in visually similar environments.

Parental attitudes toward BB and pellet guns.

As well as describing our pediatric BB and pellet gun injuries and the circumstances surrounding these injuries, we also evaluated parental perceptions of the dangers of BB and pellet guns. A convenience sample of three groups of parents and their children presenting to a Midwest, urban, children's hospital emergency department was prospectively enrolled. The three groups of parents included the injured group, which consisted of the parents whose children had been injured by BB or pellet guns; the gun group, which consisted of the parents who allowed their children to possess BB or pellet guns but had not sustained injury from these guns; and the no gun group, which consisted of the parents who did not allow their children to have these guns. All parents completed a survey concerning their attitudes toward BB and pellet guns. Twenty-eight parents completed questionnaires in each of the three groups. Most BB and pellet gun injuries occurred in adolescent males at home without adult supervision and were inflicted by a friend or by themselves. The injured group and the no gun group viewed BB and pellet guns as significantly more dangerous than the gun group. Parents who allow their children to have BB or pellet guns appear to misperceive their potential for injury by allowing their children to use these guns in an unsafe manner. Clinicians must educate parents about the significant potential for injury of nonpowdered guns.

A comparison of the initial to the later stream urine in children catheterized to evaluate for a urinary tract infection.

BACKGROUND: To avoid potential contamination, it is recommended that the first few drops of urine be discarded when obtaining a catheterized urine sample from a child being evaluated for a urinary tract infection (UTI). The existing evidence to make such a recommendation is scant. Our goal, therefore, was to determine whether the urinalysis, Gram stain, and culture results were significantly different from the initial and later urine samples collected from catheterized children. METHODS: A prospective diagnostic discrimination between early and later urine samples was conducted on a convenience sample of pediatric patients being evaluated for a UTI in an urban emergency department. Results of the urinalysis, Gram stain, and quantitative culture were compared between the early and later stream urine samples. RESULTS: Data from 86 children were analyzed. Four of 80 patients had a false identification of low colony count bacteruria from the early but not from the later stream. For patients with negative cultures, the early stream was also more likely to falsely identify > or =5 wbc/hpf (P<0.01) or bacteruria (P<0.05) on urinalysis than the later stream. CONCLUSIONS: There is a small but potentially meaningful contamination of the early stream urine compared with the later stream in young children catheterized to evaluate for a urinary tract infection.

A model of hippocampally dependent navigation, using the temporal difference learning rule.

This paper presents a model of how hippocampal place cells might be used for spatial navigation in two watermaze tasks: the standard reference memory task and a delayed matching-to-place task. In the reference memory task, the escape platform occupies a single location and rats gradually learn relatively direct paths to the goal over the course of days, in each of which they perform a fixed number of trials. In the delayed matching-to-place task, the escape platform occupies a novel location on each day, and rats gradually acquire one-trial learning, i.e., direct paths on the second trial of each day. The model uses a local, incremental, and statistically efficient connectionist algorithm called temporal difference learning in two distinct components. The first is a reinforcement-based "actor-critic" network that is a general model of classical and instrumental conditioning. In this case, it is applied to navigation, using place cells to provide information about state. By itself, the actor-critic can learn the reference memory task, but this learning is inflexible to changes to the platform location. We argue that one-trial learning in the delayed matching-to-place task demands a goal-independent representation of space. This is provided by the second component of the model: a network that uses temporal difference learning and self-motion information to acquire consistent spatial coordinates in the environment. Each component of the model is necessary at a different stage of the task; the actor-critic provides a way of transferring control to the component that performs best. The model successfully captures gradual acquisition in both tasks, and, in particular, the ultimate development of one-trial learning in the delayed matching-to-place task. Place cells report a form of stable, allocentric information that is well-suited to the various kinds of learning in the model.

Information processing with population codes.

Information is encoded in the brain by populations or clusters of cells, rather than by single cells. This encoding strategy is known as population coding. Here we review the standard use of population codes for encoding and decoding information, and consider how population codes can be used to support neural computations such as noise removal and nonlinear mapping. More radical ideas about how population codes may directly represent information about stimulus uncertainty are also discussed.