Natural disaster alters the adaptive benefits of sociality in a primate.

Weather-related disasters can radically alter ecosystems. When disaster-driven ecological damage persists, the selective pressures exerted on individuals can change, eventually leading to phenotypic adjustments. For group-living animals, social relationships are believed to help individuals cope with environmental challenges and may be a critical mechanism enabling adaptation to ecosystems degraded by disasters. Yet, whether natural disasters alter selective pressures on patterns of social interactions and whether group-living animals can, as a result, adaptively change their social relationships remains untested. Here, we leveraged unique data collected on rhesus macaques from 5 years before to 5 years after a category 4 hurricane, leading to persistent deforestation which exacerbated monkeys' exposure to intense heat. In response, macaques increased tolerance for and decreased aggression toward other monkeys, facilitating access to scarce shade critical for thermoregulation. Social tolerance predicted individual survival for 5 years after the hurricane, but not before it, revealing a clear shift in the adaptive function of social relationships in this population. We demonstrate that an extreme climatic event altered selection on sociality and triggered substantial and persistent changes in the social structure of a primate species. Our findings unveil the function and adaptive flexibility of social relationships in degraded ecosystems and identify natural disasters as potential evolutionary drivers of sociality. One-Sentence Summary: Testard et al. show that a natural disaster altered selection on sociality in group-living primates triggering persistent changes in their social structure.

Persistent social isolation reflects identity and social context but not maternal effects or early environment.

Individuals who are well integrated into society have greater access to resources and tend to live longer. Why some individuals are socially isolated and others are not is therefore puzzling from an evolutionary perspective. Answering this question requires establishing the mix of intrinsic and contextual factors that contribute to social isolation. Using social network data spanning up to half of the median adult lifespan in a gregarious primate, we found that some measures of social isolation were modestly repeatable within individuals, consistent with a trait. By contrast, social isolation was not explained by the identity of an animal's mother or the group into which it was born. Nevertheless, age, sex and social status each played a role, as did kin dynamics and familiarity. Females with fewer close relatives were more isolated, and the more time males spent in a new group the less isolated they became, independent of their social status. These results show that social isolation results from a combination of intrinsic and environmental factors. From an evolutionary perspective, these findings suggest that social isolation could be adaptive in some contexts and partly maintained by selection.

Family network size and survival across the lifespan of female macaques.

Two decades of research suggest social relationships have a common evolutionary basis in humans and other gregarious mammals. Critical to the support of this idea is growing evidence that mortality is influenced by social integration, but when these effects emerge and how long they last is mostly unknown. Here, we report in adult female macaques that the impact of number of close adult female relatives, a proxy for social integration, on survival is not experienced uniformly across the life course; prime-aged females with a greater number of relatives had better survival outcomes compared with prime-aged females with fewer relatives, whereas no such effect was found in older females. Group size and dominance rank did not influence this result. Older females were less frequent targets of aggression, suggesting enhanced experience navigating the social landscape may obviate the need for social relationships in old age. Only one study of humans has found age-based dependency in the association between social integration and survival. Using the largest dataset for any non-human animal to date, our study extends support for the idea that sociality promotes survival and suggests strategies employed across the life course change along with experience of the social world.

A Primer on Foraging and the Explore/Exploit Trade-Off for Psychiatry Research.

Foraging is a fundamental behavior, and many types of animals appear to have solved foraging problems using a shared set of mechanisms. Perhaps the most common foraging problem is the choice between exploiting a familiar option for a known reward and exploring unfamiliar options for unknown rewards-the so-called explore/exploit trade-off. This trade-off has been studied extensively in behavioral ecology and computational neuroscience, but is relatively new to the field of psychiatry. Explore/exploit paradigms can offer psychiatry research a new approach to studying motivation, outcome valuation, and effort-related processes, which are disrupted in many mental and emotional disorders. In addition, the explore/exploit trade-off encompasses elements of risk-taking and impulsivity-common behaviors in psychiatric disorders-and provides a novel framework for understanding these behaviors within an ecological context. Here we explain relevant concepts and some common paradigms used to measure explore/exploit decisions in the laboratory, review clinically relevant research on the neurobiology and neuroanatomy of explore/exploit decision making, and discuss how computational psychiatry can benefit from foraging theory.

Genetic influences on social attention in free-ranging rhesus macaques.

An ethological approach to attention predicts that organisms orient preferentially to valuable sources of information in the environment. For many gregarious species, orienting to other individuals provides valuable social information but competes with food acquisition, water consumption and predator avoidance. Individual variation in vigilance behaviour in humans spans a continuum from inattentive to pathological levels of interest in others. To assess the comparative biology of this behavioural variation, we probed vigilance rates in free-ranging macaques during water drinking, a behaviour incompatible with the gaze and postural demands of vigilance. Males were significantly more vigilant than females. Moreover, vigilance showed a clear genetic component, with an estimated heritability of 12%. Monkeys carrying a relatively infrequent 'long' allele of TPH2, a regulatory gene that influences serotonin production in the brain, were significantly less vigilant compared to monkeys that did not carry the allele. These findings resonate with the hypothesis that the serotonin pathway regulates vigilance in primates and by extension provoke the idea that individual variation in vigilance and its underlying biology may be adaptive rather than pathological.

A physiologically-inspired model of numerical classification based on graded stimulus coding.

In most natural decision contexts, the process of selecting among competing actions takes place in the presence of informative, but potentially ambiguous, stimuli. Decisions about magnitudes - quantities like time, length, and brightness that are linearly ordered - constitute an important subclass of such decisions. It has long been known that perceptual judgments about such quantities obey Weber's Law, wherein the just-noticeable difference in a magnitude is proportional to the magnitude itself. Current physiologically inspired models of numerical classification assume discriminations are made via a labeled line code of neurons selectively tuned for numerosity, a pattern observed in the firing rates of neurons in the ventral intraparietal area (VIP) of the macaque. By contrast, neurons in the contiguous lateral intraparietal area (LIP) signal numerosity in a graded fashion, suggesting the possibility that numerical classification could be achieved in the absence of neurons tuned for number. Here, we consider the performance of a decision model based on this analog coding scheme in a paradigmatic discrimination task - numerosity bisection. We demonstrate that a basic two-neuron classifier model, derived from experimentally measured monotonic responses of LIP neurons, is sufficient to reproduce the numerosity bisection behavior of monkeys, and that the threshold of the classifier can be set by reward maximization via a simple learning rule. In addition, our model predicts deviations from Weber Law scaling of choice behavior at high numerosity. Together, these results suggest both a generic neuronal framework for magnitude-based decisions and a role for reward contingency in the classification of such stimuli.

Application of neurosonography to experimental physiology.

When Horsley and Clark invented the stereotaxic technique they revolutionized experimental neurobiology. For the first time it became possible to repeatably place experimental or surgical probes at precise locations within the skull. Unfortunately, variations in the position and size of neuroanatomical structures within the cranium have always limited the efficiency of this technology. Recent advances in diagnostic medical ultrasonography, however, allow for the real-time visualization of anatomical structures, in some cases with resolutions of up to 150 microm. We report here that commercially available ultrasonographs can be used in the laboratory to generate real-time in vivo images of brain structures in both anesthetized and awake-behaving animals. We found that ultrasonic imaging is compatible with many types of experimental probes including single neuron recording electrodes, microinjection pipettes, and electrodes for producing electrolytic lesions. Ultrasonic imaging can be used to place, monitor and visualize these probes in vivo. In our hands, commercially available ultrasonic probes designed for pediatric use allowed us to visualize anatomical structures with sub-millimeter resolution in primate brains. Finally, ultrasonic imaging allowed us to reduce the risk of accidentally damaging major blood vessels, greatly reducing the incidence of stroke as an unintended complication of an experimental neurosurgical procedure. Diagnostic ultrasound holds the promise of reducing the uncertainty associated with stereotaxic surgery, an improvement which would significantly improve the efficiency of many neurobiological investigations, reducing the number of animal subjects employed in this research. While this demonstration focuses on sonographic imaging in non-human primates, similar advances should also be possible for studies in other species, including rodents.

Short-term changes in movement frequency do not alter the spatial tuning of saccade-related neurons in intraparietal cortex.

Modulations of the firing rates of neurons in the lateral intraparietal area (LIP) have been observed during experiments designed to examine decision-processing, movement planning, and visual attention. These modulations have been assumed to reflect a uniform scaling of spatially stationary response fields, which describe firing rate as a function of either visual target location or movement metrics. However, because complete response fields are rarely collected, the possibility exists that these modulations may reflect shifts in response field location or changes in response field size. Moreover, many of these observed changes in LIP neuronal activity are also correlated with experimental practices that alter the frequency with which particular visual stimuli are viewed and particular movements are produced. The effects of repeatedly presenting a particular target and eliciting a particular movement on the response fields of LIP neurons warrant closer inspection because manipulations of this type are known to alter both the location and size of the receptive fields of many cortical sensory neurons. To address this issue, we measured the response fields of neurons in intraparietal cortex under two conditions over a period of up to 2 h: one in which each of nearly 200 stimulus locations was equally likely to serve as the saccade target on a trial, and a second in which one stimulus location was up to 750 times likelier to serve as the saccade target on a trial than were any of the other stimulus locations. We found no shifts in response field location or changes in response field size when we altered the frequency with which particular movements were produced or particular visual stimuli were presented. These data suggest that the response fields of intraparietal neurons are stationary over short periods of time and under conditions similar to those typically used to study LIP neuronal activity.

Neural correlates of decision variables in parietal cortex.

Decision theory proposes that humans and animals decide what to do in a given situation by assessing the relative value of each possible response. This assessment can be computed, in part, from the probability that each action will result in a gain and the magnitude of the gain expected. Here we show that the gain (or reward) a monkey can expect to realize from an eye-movement response modulates the activity of neurons in the lateral intraparietal area, an area of primate cortex that is thought to transform visual signals into eye-movement commands. We also show that the activity of these neurons is sensitive to the probability that a particular response will result in a gain. When animals can choose freely between two alternative responses, the choices subjects make and neuronal activation in this area are both correlated with the relative amount of gain that the animal can expect from each response. Our data indicate that a decision-theoretic model may provide a powerful new framework for studying the neural processes that intervene between sensation and action.

QT dispersion as a noninvasive predictor of inducible ventricular tachycardia.

The QT dispersion (QTD) on the surface electrocardiogram is a noninvasive marker of heterogeneity of ventricular repolarization. An increased QTD has been associated with spontaneous ventricular arrhythmias. We investigated the relationship of QTD to inducible reentrant sustained ventricular tachycardia (VT) in 66 patients who underwent programmed electrical stimulation. Thirty-three patients had inducible VT and 33 had noninducible VT with up to three extra stimuli. The QTD was significantly longer in patients with inducible VT (79+/-30 ms) compared with those in whom VT was noninducible (50+/-20 ms, P < .0001). QTD of > or =70 ms had a sensitivity of 67%, a specificity of 94%, a positive predictive value of 92%, and a negative predictive value of 74% for inducible VT. We conclude that QTD is an easily measurable electrocardiographic index that is increased in patients with inducible VT, and a QTD of > or =70 ms is highly predictive of VT inducibility.

Response fields of intraparietal neurons quantified with multiple saccadic targets.

The activity of each of 99 intraparietal neurons was studied in three awake-behaving rhesus monkeys (Macaca mulatta) while subjects performed 100-900 delayed saccade trials. On each trial, a saccadic target was presented at one location selected randomly from a grid of 441 locations spanning 40 degrees of horizontal and vertical visual space. Individual neurons in our population were sensitive to both the direction and amplitude of saccades. Response fields, which plotted firing rate as a function of the horizontal and vertical amplitude of movements for each neuron, were characterized by a Cartesian two-dimensional gaussian model. The goodness-of-fit of these gaussian models was tested by: (1) comparing observed responses with predicted responses for each movement; and (2) by computing the percentage of variance explained by each model. Cartesian Gaussian models provided a good fit to the response fields of most neurons. Across our population, the Gaussian fit to the response field of each neuron accounted for more of the variance in neuronal activity when the data were plotted with regard to the horizontal and vertical amplitude of the saccade than when the same data were plotted with regard to the position of the saccadic target. The Gaussian functions were used to estimate the eccentricity and spatial tuning breadth of each neuronal response field. Modal response field radius was less than 5 degrees, whereas mean response field radius was about 10 degrees. Linear regression analysis demonstrated that response field eccentricity accounted for less than 30% of the variance in response field radius. Analysis of the horizontal distribution of response field centers showed an approximately normal distribution around central fixation. Most histologically recovered neurons were located on the lateral bank of the intraparietal sulcus, although a small number of saccade-related neurons were recorded from Brodmann's area 5 on the medial bank of the intraparietal sulcus.

Responses of intraparietal neurons to saccadic targets and visual distractors.

Current evidence suggests that neuronal activity in the lateral intraparietal area (LIP) reflects sensory-motor processes, but it remains unclear whether LIP activation participates directly in the planning of future eye movements or encodes data about both sensory events and the behavioral significance of those sensory events. To examine this issue, 31 intraparietal neurons were studied in awake, behaving monkeys trained to perform two tasks that independently controlled the location of a saccadic target and the location and behavioral relevance of a visual distractor. In both of these tasks, two eccentric light-emitting diodes (LEDs) were illuminated yellow, one above and one below a fixation stimulus. Shortly after the eccentric LEDs were illuminated, a change in the color of the fixation stimulus indicated which of these LEDs served as the saccadic goal and which served as a visual distractor. In the first or distractor-irrelevant task, fixation offset indicated that the subject must initiate a saccade shifting gaze to the saccadic goal. In the second or distractor-relevant task, distractor offset served as the saccade initiation cue. Intraparietal neurons responded more strongly in association with an LED that served as a saccadic target than in association with the same LED when it served as a visual distractor. Neuronal responses in association with either target or distractor stimuli on distractor-relevant and distractor-irrelevant blocks of trials were statistically indistinguishable. When the location of either the target or the distractor was varied across trials, the response of each neuron in association with a particular stimulus location was always greater for targets than for distractors and the magnitude of this response difference was independent of distractor relevance; however, distractors were nearly always associated with some intraparietal neuronal activity. A target/distractor selectivity index was computed for each neuron as the difference between responses associated with targets minus responses associated with distractors divided by the sum of these values. When the selectivity of each neuron on the distractor-relevant task was plotted against the selectivity of the same neuron on the distractor-irrelevant task, activity in the population of intraparietal neurons was found to be independent of distractor relevance. These data suggest that LIP neuronal activation represents saccadic targets and, at a lower level of activity, visual distractors, but does not encode the relevance of distractor stimuli on these tasks.

Flecainide acetate for paroxysmal supraventricular tachyarrhythmias. The Flecainide Supraventricular Tachycardia Study Group.

Flecainide has been shown to be effective in short-term, controlled studies for prevention of paroxysmal supraventricular tachycardia (SVT) and paroxysmal atrial fibrillation (AF). However, it is unknown whether this beneficial response is maintained during long-term chronic therapy. Forty-nine patients were studied who enrolled in double-blind, placebo-controlled, short-term studies of safety and efficacy and subsequently received long-term, open-label therapy for > or = 6 months (mean duration of therapy, 17 months). To evaluate chronic efficacy, events during long-term therapy were documented by a transtelephonic monitor for either 4 or 8 weeks, comparable to the corresponding 4- or 8-week placebo-baseline periods in the same patients. Results during chronic therapy were compared with those at baseline and after the initial (short-term) treatment period. Compared with placebo-baseline results, the number of patients free of arrhythmic attacks increased significantly for both patients with SVT (from 24% to 82%, p = 0.013, n = 17) and patients with AF (from 12% to 68%, p < 0.001, n = 25). Mean time to first attack and mean number of days between attacks also showed significant and parallel increases during the chronic efficacy period. In patients with paired short- and long-term efficacy evaluations with the same dose of flecainide, end points were maintained at equivalent levels or showed further improvement (i.e., mean rate of AF attacks decreased further with chronic therapy, p = 0.036). No proarrhythmic events, death, or myocardial infarction occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

A possible ontogenic etiology for idiopathic left varicocele.

A total of 659 consecutive patients underwent venography for the evaluation of idiopathic left varicocele before sclerotherapy. In 484 cases no valves of the left spermatic vein could be demonstrated, while 172 patients demonstrated competent valves or absent insertions of the left spermatic vein at the typical point on the left renal vein plus retrograde flow over persistent intercardinal anastomoses. Stenosis of the renal vein occurred in 103 patients (15.7%). In only 3 patients was stenosis observed in the course of the left iliac vein, suggestive of the so-called distal nutcracker phenomenon. We propose that during embryogenesis disturbances in the development of the secondary venous system may result in the idiopathic left varicocele.

Flecainide acetate treatment of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation: dose-response studies. The Flecainide Supraventricular Tachycardia Study Group.

The dose-response relations for efficacy and tolerance of the antiarrhythmic drug flecainide acetate were studied in 28 patients with paroxysmal supraventricular tachycardia (Group 1) and 45 patients with paroxysmal atrial fibrillation or flutter (Group 2). Recurrent symptomatic tachycardia was documented with use of transtelephonic electrocardiographic recording. Patients received flecainide in doses of 25, 50, 100 and 150 mg twice daily and placebo for 1 month treatment periods. Among 14 patients in Group 1 who qualified for efficacy analysis, 4 (29%) had no tachycardia while taking placebo. The number with no tachycardia increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 12 (86%) of 14 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Among 28 patients in Group 2, 2 (7%) had no tachycardia while taking placebo. The number with no tachycardia also increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 17 (61%) of 28 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Noncardiac adverse experiences were the leading cause of premature study discontinuation during flecainide treatment periods (five patients in Group 1 and six patients in Group 2).

Eosinophilic ureteritis associated with eosinophilic cholangitis: a case report.

Eosinophilic infiltrate of the urinary tract is rare. We report on a patient with eosinophilic cholangitis who later had eosinophilic ureteritis. This case emphasizes the potential serious nature of eosinophilic ureteritis, which often presents with complete ureteral obstruction. The literature pertaining to eosinophilic ureteritis and eosinophilic biliary disease is reviewed.

Efficacy and tolerance of Ethmozine (moricizine HCl) in placebo-controlled trials.

To investigate the tolerance and efficacy of moricizine HCl, single-blind placebo-controlled trials were conducted. The early protocols involved patients hospitalized for 14 days, and daily Holter monitoring was used to document efficacy and the degree of spontaneous variability of ventricular premature complexes (VPCs). Moricizine HCl was given orally from 2.9 to 15.3 mg/kg 3 times daily. Patients with lethal ventricular arrhythmias were excluded. Additional outpatient trials were conducted to define long-term efficacy and safety. A dose-response relation between moricizine HCl and the percentage of reduction in frequency of benign or potentially lethal ventricular arrhythmias was documented. Eighty-five percent of patients achieved a reduction in VPCs greater than 75% with daily dosages ranging from 10.1 to 15 mg/kg. This corresponded to a 95% decrease in mean frequency of VPCs. Long-term studies demonstrated no evidence of compromise in left ventricular function, and the proarrhythmic rate was only 2%. Symptomatic side effects were mild and usually well tolerated. Nausea, the most common, occurred in 11% of patients and dizziness in 9%. These results indicate that moricizine HCl is an effective and well-tolerated antiarrhythmic agent.

Rapid bacteriuria screening in a urological setting: clinical use.

The clinical use of a commercially available semiautomated bacteriuria screening device was evaluated in a urological setting. The 1,300 consecutive urine specimens processed by the device were contrasted with results of standard semiquantitative culture. A small number (2 per cent) were screened unsuccessfully owing to a clogged filter. With greater than 10(5) colony-forming units per ml. the sensitivity of the device was 91 per cent but it was only 81 per cent with bacteriuria levels greater than 10(4) colony-forming units per ml. More importantly, the predictive value of a negative test was 99 per cent with more than 10(5) colony-forming units per ml. and 96 per cent with more than 10(4) colony-forming units per ml. This capability promotes safe urological instrumentation and timely patient care.