Behavioral Response Patterns Research Articles

Kinetics and Dose Dependency of Intranasal Oxytocin Effects on Amygdala Reactivity

BackgroundCurrent neuroimaging perspectives on a variety of mental disorders emphasize dysfunction of the amygdala. The neuropeptide oxytocin (OXT), a key mediator in the regulation of social cognition and behavior, accumulates in cerebrospinal fluid after intranasal administration in macaques and humans and modulates amygdala reactivity in both species. However, the translation of neuromodulatory OXT effects to novel treatment approaches is hampered by the absence of studies defining the most effective dose and dose–response latency for targeting the amygdala. MethodsTo address this highly relevant issue, a total of 116 healthy men underwent functional magnetic resonance imaging using a randomized, double-blind, placebo-controlled crossover study design. The experimental rationale was to systematically vary dose–test latencies (15–40, 45–70, and 75–100 minutes) and doses of OXT (12, 24, and 48 international units) in order to identify the most robust effects on amygdala reactivity. During functional magnetic resonance imaging, subjects completed an emotional face recognition task including stimuli with varying intensities ranging from low (highly ambiguous) to high (less ambiguous). ResultsOur results indicate that the OXT-induced inhibition of amygdala responses to fear was most effective in a time window between 45 and 70 minutes after administration of a dose of 24 international units. Furthermore, the observed effect was most evident in subjects scoring high on measures of autistic-like traits. Behavioral response patterns suggest that OXT specifically reduced an emotional bias in the perception of ambiguous faces. ConclusionsThese findings provide initial evidence of the most effective dose and dose–test interval for future experimental or therapeutic regimens aimed at targeting amygdala functioning using intranasal OXT administration.

The defensive behavioral patterns of captive white-lipped and collared peccary (Mammalia, Tayassuidae): an approach for conservation of the species

Defensive behavioral patterns in response to human-induced rapid environmental change can affect animals’ fitness and may play a role in species conservation status. To test this hypothesis, we compared the risk assessment and defensive behavioral responses of captive white-lipped peccary (WLP; Tayassu pecari) and collared peccary (CP; Pecari tajacu), which retain different conservation status; WLP are considered vulnerable and CP of least concern. We used an adapted paradigm of the mouse defense test battery (MDTB) comprising four consecutive tests. Two of these tests simulated a novel environment, while the other two stimulated the expression of defensive behavioral patterns. Besides differences in risk assessment and defensive threat/attack behavioral patterns between species, we compared flight initiation distance, flight speed, and plasma glucocorticoid concentrations. When facing a novel environment and risk challenges from humans’ predator-like cues, the white-lipped peccary showed more exploratory and defensive threat/attack behavioral patterns, shorter flight initiation distances, and lower flight speeds, whereas the collared peccaries showed more cautious and retreat patterns, longer flight initiation distances, and higher flight speeds. There were also correlations between physiological and behavioral parameters. We confirmed our hypothesis that the collared peccary’s cautiousness may help to prevent a decrease in its population, while the white-lipped peccary’s exploratory and confrontational behavioral patterns in overhunted areas, together with other simultaneous factors as forest fragmentation, might contribute to placing this species in the vulnerable category.

Distinct Neural Signatures for Very Small and Very Large Numerosities.

Behavioral studies of numerical cognition have shown that perceptual threshold for numerosity discrimination depends on the range of numerical values to be estimated. Discrimination threshold is constant when comparing very small numerosities via the mechanism called subitizing, while it increases as a function of numerosity for numbers beyond that range governed by subitizing. However, when numerosity gets so large that the individual elements start to form a cluttered ensemble, discrimination threshold increases as a function of the square root of numerosity. These behavioral patterns suggest that our sense of number is not based on a unitary mechanism and is rather based on multiple numerosity processing mechanisms depending on the absolute numerosity to be estimated. In this study, we demonstrate neurophysiological evidence for such multiple mechanisms. Participants’ electroencephalogram (EEG) was recorded while they viewed arrays containing either very small (1–4) or very large (100–400) number of dots with systematic variations in non-numerical cues. A linear model that tested the effects of numerical and non-numerical cues on the visual-evoked potentials (VEPs) revealed strong neural sensitivity to numerosity around 160–180 ms over right occipito-parietal sites irrespective of the numerical range presented. In contrast, earlier neural responses (~100 ms) showed markedly distinct patterns across the different numerical ranges tested. These results indicate that differences in behavioral response patterns in numerosity estimation across various numerical ranges may arise from the differences in the first stages of visual analysis. Collectively, the findings provide a firmer ground for the idea that there exists a brain system specifically dedicated for numerosity processing, yet they also suggest that multiple early visual cortical mechanisms converge to that numerosity processing stage later in the visual stream.

Price and Income Elasticities of Residential Energy Demand in Germany

We apply a quadratic expenditure system to estimate price and expenditure elasticities of residential energy demand (electricity and heating) in Germany. Using official expenditure data from 1993 to 2008, we estimate an expenditure elasticity for electricity of 0.3988 and of 0.4055 for space heating. The own price elasticity for electricity is -0.4310 and -0.5008 in the case of space heating. Disaggregation of households by expenditure and demographic composition reveals that the behavioural response to energy price changes is weaker (stronger) for low-income (top-income) households. There are considerable economies of scale in residential energy use but scale effects are not well approximated by the new OEDC equivalence scale. Real increases in energy prices show a regressive pattern of incidence, implying that the welfare consequences of direct energy taxation are larger for low income households. The application of zero-elasticities in assessments of welfare consequences of energy taxation strongly underestimates potential welfare effects. The increase in inequality is 22% smaller when compared to the application of rich and disaggregated behavioural response patterns as estimated in this paper.

Zinc Tempers Haloperidol-induced Behavioural Changes in Healthy Mice

Objective: Behavioural changes secondary to haloperidol/zinc administration were studied, with a view to understanding the patterns of behavioural responses that may be exhibited after such treatment in healthy mice. Methodology: 6 month old Swiss mice (24-30 g each, n=12), were given vehicle (distilled water), haloperidol (2 mg/kg), zinc (as Zinc gluconate, 2.5 and 5 mg/kg) or haloperidol/zinc combination, orally for 21 days. Behaviours were assessed after the first and last dose of haloperidol/zinc. Results: Zinc administration led to a significant reduction of haloperidol-induced suppression of horizontal locomotion, rearing and grooming behaviours. Zn also prevented the deterioration in Y-maze and radial-arm maze working-memory that was associated with repeated haloperidol administration. Finally, an enhanced anxiolytic effect was seen with co-administration of haloperidol with the lower dose of zinc. Conclusion: Co-administration of haloperidol with zinc can reduce some unwanted effects that are known to be associated with haloperidol therapy; hence zinc may be a beneficial adjunct to haloperidol administration.

Sex differences in behavioral and PKA cascade responses to repeated cocaine administration.

Previous studies have shown sex different patterns in behavioral responses to cocaine. Here, we used between-subject experiment design to study whether sex differences exist in the development of behavioral sensitization and tolerance to repeated cocaine, as well as the role of protein kinase A (PKA) signaling cascade in this process. Ambulatory and rearing responses were recorded in male and female rats after 1 to 14days of administration of saline or cocaine (15mg/kg; ip). Correspondent PKA-associated signaling in the nucleus accumbens (NAc) and caudate-putamen (CPu) was measured at each time point. Our results showed that females exhibited higher cocaine-induced behavioral responses and developed behavioral sensitization and tolerance faster than males. Whereas females developed behavioral sensitization to cocaine after 2days and tolerance after 14days, male rats developed sensitization after 5days. In addition, cocaine induced a sexual dimorphic pattern in the progression of neuronal adaptations on the PKA cascade signaling in region (NAc vs. CPu) and time (days of cocaine administration)-dependent manners. In general, more PKA signaling cascade changes were found in the NAc of males on day 5 and in the CPu of females with repeated cocaine injection. In addition, in females, behavioral activities positively correlated with FosB levels in the NAc and CPu and negatively correlated with Cdk5 and p35 in the CPu, while no correlation was observed in males. Our studies suggest that repeated cocaine administration induced different patterns of behavioral and molecular responses in the PKA cascade in male and female rats.

A farewell to brake reaction times? Kinematics-dependent brake response in naturalistic rear-end emergencies

Driver braking behavior was analyzed using time-series recordings from naturalistic rear-end conflicts (116 crashes and 241 near-crashes), including events with and without visual distraction among drivers of cars, heavy trucks, and buses. A simple piecewise linear model could be successfully fitted, per event, to the observed driver decelerations, allowing a detailed elucidation of when drivers initiated braking and how they controlled it. Most notably, it was found that, across vehicle types, driver braking behavior was strongly dependent on the urgency of the given rear-end scenario⿿s kinematics, quantified in terms of visual looming of the lead vehicle on the driver⿿s retina. In contrast with previous suggestions of brake reaction times (BRTs) of 1.5s or more after onset of an unexpected hazard (e.g., brake light onset), it was found here that braking could be described as typically starting less than a second after the kinematic urgency reached certain threshold levels, with even faster reactions at higher urgencies. The rate at which drivers then increased their deceleration (towards a maximum) was also highly dependent on urgency. Probability distributions are provided that quantitatively capture these various patterns of kinematics-dependent behavioral response. Possible underlying mechanisms are suggested, including looming response thresholds and neural evidence accumulation. These accounts argue that a naturalistic braking response should not be thought of as a slow reaction to some single, researcher-defined ⿿hazard onset⿿, but instead as a relatively fast response to the visual looming cues that build up later on in the evolving traffic scenario.

Patterns of Adolescent Regulatory Responses During Family Conflict and Mental Health Trajectories.

Four distinct patterns of adolescents' behavioral, emotional, and physiological responses to family conflict were identified during mother-father-adolescent (M=13.08years) interactions. Most youth displayed adaptively regulated patterns comprised of low overt and subjective distress. Under-controlled adolescents exhibited elevated observable and subjective anger. Over-controlled adolescents were withdrawn and reported heightened subjective distress. Physiologically reactive adolescents had elevated cortisol coupled with low overt and subjective distress. Regulation patterns were associated with unique mental health trajectories. Under-controlled adolescents had elevated conduct and peer problems whereas over-controlled adolescents had higher anxiety and depressive symptoms. Physiologically reactive adolescents had low concurrent, but increasing levels of depressive, anxiety, and peer problem symptoms. Findings underscore the importance of examining organizations of regulatory strategies in contributing to adolescent mental health.

Vasopressin differentially modulates aggression and anxiety in adolescent hamsters administered anabolic steroids

Adolescent Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids display increased offensive aggression and decreased anxiety correlated with an increase in vasopressin afferent development, synthesis, and neural signaling within the anterior hypothalamus. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts as hamsters display decreased offensive aggression and increased anxiety correlated with a decrease in anterior hypothalamic vasopressin. This study investigated the hypothesis that alterations in anterior hypothalamic vasopressin neural signaling modulate behavioral shifting between adolescent anabolic/androgenic steroid-induced offensive aggression and anxiety. To test this, adolescent male hamsters were administered anabolic/androgenic steroids and tested for offensive aggression or anxiety following direct pharmacological manipulation of vasopressin V1A receptor signaling within the anterior hypothalamus. Blockade of anterior hypothalamic vasopressin V1A receptor signaling suppressed offensive aggression and enhanced general and social anxiety in hamsters administered anabolic/androgenic steroids during adolescence, effectively reversing the pattern of behavioral response pattern normally observed during the adolescent exposure period. Conversely, activation of anterior hypothalamic vasopressin V1A receptor signaling enhanced offensive aggression in hamsters exposed to anabolic/androgenic steroids during adolescence. Together, these findings suggest that the state of vasopressin neural development and signaling in the anterior hypothalamus plays an important role in behavioral shifting between aggression and anxiety following adolescent exposure to anabolic/androgenic steroids.

Distinctive cardiac autonomic dysfunction following stress exposure in both sexes in an animal model of PTSD

It is unclear whether the poor autonomic flexibility or dysregulation observed in patients with posttraumatic stress disorder (PTSD) represents a pre-trauma vulnerability factor or results from exposure to trauma. We used an animal model of PTSD to assess the association between the behavioral response to predator scent stress (PSS) and the cardiac autonomic modulation in male and female rats.The rats were surgically implanted with radiotelemetry devices to measure their electrocardiograms and locomotor activity (LMA). Following baseline telemetric monitoring, the animals were exposed to PSS or sham-PSS. Continuous telemetric monitoring (24h/day sampling) was performed over the course of 7days. The electrocardiographic recordings were analyzed using the time- and frequency-domain indexes of heart rate variability (HRV). The behavioral response patterns were assessed using the elevated plus maze and acoustic startle response paradigms for the retrospective classification of individuals according to the PTSD-related cut-off behavioral criteria.During resting conditions, the male rats had significantly higher heart rates (HR) and lower HRV parameters than the female rats during both the active and inactive phases of the daily cycle. Immediately after PSS exposure, both the female and male rats demonstrated a robust increase in HR and a marked drop in HRV parameters, with a shift of sympathovagal balance towards sympathetic predominance. In both sexes, autonomic system habituation and recovery were selectively inhibited in the rats whose behavior was extremely disrupted after exposure to PSS. However, in the female rats, exposure to the PSS produced fewer EBR rats, with a more rapid recovery curve than that of the male rats. PSS did not induce changes to the circadian rhythm of the LMA.According to our results, PTSD can be conceptualized as a disorder that is related to failure-of-recovery mechanisms that impede the restitution of physiological homeostasis.

Effect of calorie restriction on spontaneous physical activity and body mass in mice divergently selected for basal metabolic rate (BMR)

Spontaneous physical activity (SPA) represents an important component of daily energy expenditures in animals and humans. Intra-specific variation in SPA may be related to the susceptibility to metabolic disease or obesity. In particular, reduced SPA under conditions of limited food availability may conserve energy and prevent loss of body and fat mass (‘thrifty genotype hypothesis’). However, both SPA and its changes during food restriction show wide inter-individual variations. We studied the effect of 30% caloric restriction (CR) on SPA in laboratory mice divergently selected for high (H-BMR) and low (L-BMR) basal metabolic rate. Selection increased SPA in the H-BMR line but did not change it in the L-BMR mice. This effect reflected changes in SPA intensity but not SPA duration. CR increased SPA intensity more strongly in the L-BMR line than in the H-BMR line and significantly modified the temporal variation of SPA. However, the initial between-line differences in SPA were not affected by CR. Loss of body mass during CR did not differ between both lines. Our results show that the H-BMR mice can maintain their genetically determined high SPA under conditions of reduced food intake without sacrificing their body mass. We hypothesize that this pattern may reflect the higher flexibility in the energy budget in the H-BMR line, as we showed previously that mice from this line reduced their BMR during CR. These energy savings may allow for the maintenance of elevated SPA in spite of reduced food intake. We conclude that the effect of CR on SPA is in large part determined by the initial level of BMR, whose variation may account for the lack of universal pattern of behavioural responses to CR.

Controlled Low-Pressure Blast-Wave Exposure Causes Distinct Behavioral and Morphological Responses Modelling Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Comorbid Mild Traumatic Brain Injury-Post-Traumatic Stress Disorder.

The intense focus in the clinical literature on the mental and neurocognitive sequelae of explosive blast-wave exposure, especially when comorbid with post-traumatic stress-related disorders (PTSD) is justified, and warrants the design of translationally valid animal studies to provide valid complementary basic data. We employed a controlled experimental blast-wave paradigm in which unanesthetized animals were exposed to visual, auditory, olfactory, and tactile effects of an explosive blast-wave produced by exploding a thin copper wire. By combining cognitive-behavioral paradigms and ex vivo brain MRI to assess mild traumatic brain injury (mTBI) phenotype with a validated behavioral model for PTSD, complemented by morphological assessments, this study sought to examine our ability to evaluate the biobehavioral effects of low-intensity blast overpressure on rats, in a translationally valid manner. There were no significant differences between blast- and sham-exposed rats on motor coordination and strength, or sensory function. Whereas most male rats exposed to the blast-wave displayed normal behavioral and cognitive responses, 23.6% of the rats displayed a significant retardation of spatial learning acquisition, fulfilling criteria for mTBI-like responses. In addition, 5.4% of the blast-exposed animals displayed an extreme response in the behavioral tasks used to define PTSD-like criteria, whereas 10.9% of the rats developed both long-lasting and progressively worsening behavioral and cognitive "symptoms," suggesting comorbid PTSD-mTBI-like behavioral and cognitive response patterns. Neither group displayed changes on MRI. Exposure to experimental blast-wave elicited distinct behavioral and morphological responses modelling mTBI-like, PTSD-like, and comorbid mTBI-PTSD-like responses. This experimental animal model can be a useful tool for elucidating neurobiological mechanisms underlying the effects of blast-wave-induced mTBI and PTSD and comorbid mTBI-PTSD.

Can Hospital Form Trigger Fear Response?

To examine whether exposure to curve versus sharp contours in the built healthcare setting produces systematic and identifiable patterns of amygdala activation and behavioral response in healthy adults. Recent studies in cognitive neuroscience suggest that humans prefer objects with a curved contour compared with objects that have pointed features and a sharp-angled contour. An implicit perception of threat represented by sharp objects, in humans, was hypothesized to explain this bias. The study adopted a within-subject experimental design, where 36 subjects (representing three age-groups and both sexes) were exposed to a randomized order of 312 real-life images (objects, interiors, exteriors, landscape, and a set of control images). Amygdala activation was simultaneously captured using functional magnetic resonance imaging technology. Subjects' preference (like/dislike) data were also collected while in the scanner. Data were collected in 2013. In case of images depicting landscape and healthcare objects, brain scans show significant higher amygdala activation associated with sharp contours. However, in relation to images depicting hospital interiors and exterior envelops, brain scans show significant higher amygdala activation associated with curve contours. These activations pertain to exposure during the precognitive stages of the subjects' perception. Hospital forms do have systematic impact on fear response during precognitive stages of human perception. Whether this first impression colors the subsequent experience of an actual patient with real illness or injury is unknown.

Spatially Tuned Neurons in Corvid Nidopallium Caudolaterale Signal Target Position During Visual Search.

The avian pallial endbrain area nidopallium caudolaterale (NCL) shows important similarities to mammalian prefrontal cortex in connectivity, dopamine neurochemistry, and function. Neuronal processing in NCL has been studied with respect to sensory, cognitive, and reward information, but little is known about its role in more direct control of motor behavior. We investigated NCL activity during the choice period of a delayed match-to-sample task, as 2 trained crows searched and selected a previously remembered visual target among an array of 4 pictures. The crows exhibited behavioral response patterns consistent with serial visual search. Many single NCL neurons were spatially tuned to specific target positions during visual search and directed motor behavior. Moreover, single NCL neurons dynamically changed their tuning properties to represent different behaviorally relevant task variables across the trial. In consecutive task periods, single neurons responded to visual stimuli, stored stimulus information in working memory, guided goal-directed behavior depending on the remembered target picture, and encoded trial outcomes. This flexible encoding of all task-relevant aspects in the executive control of goal-directed behavior represents a striking convergence to neuronal encoding in primate prefrontal cortex. These data highlight key properties of associative endbrain areas underlying flexible cognitive behavior in corvids and primates.

Neuroethological validation of an experimental apparatus to evaluate oriented and non-oriented escape behaviours: Comparison between the polygonal arena with a burrow and the circular enclosure of an open-field test

Inhibition of GABAergic neural inputs to dorsal columns of the periaqueductal grey matter (dPAG), posterior (PH) and dorsomedial (DMH) hypothalamic nuclei elicits distinct types of escape behavioural reactions. To differentiate between the variety and intensity of panic-related behaviours, the pattern of defensive behaviours evoked by blockade of GABAA receptors in the DMH, PH and dPAG were compared in a circular open-field test and in a recently designed polygonal arena. In the circular open-field, the defensive behaviours induced by microinjection of bicuculline into DMH and PH were characterised by defensive alertness behaviour and vertical jumps preceded by rearing exploratory behaviour. On the other hand, explosive escape responses interspersed with horizontal jumps and freezing were observed after the blockade of GABAA receptors on dPAG neurons. In the polygonal arena apparatus, the escape response produced by GABAergic inhibition of DMH and PH neurons was directed towards the burrow. In contrast, the blockade of GABAA receptors in dPAG evoked non-oriented escape behaviour characterised by vigorous running and horizontal jumps in the arena. Our findings support the hypothesis that the hypothalamic nuclei organise oriented escape behavioural responses whereas non-oriented escape is elaborated by dPAG neurons. Additionally, the polygonal arena with a burrow made it easy to discriminate and characterise these two different patterns of escape behavioural responses. In this sense, the polygonal arena with a burrow can be considered a good methodological tool to discriminate between these two different patterns of escape behavioural responses and is very useful as a new experimental animal model of panic attacks.

Recall Bias in Patients with Chronic Low Back Pain: Individual Pain Response Patterns Are More Important Than Pain Itself!

Patients' cognitive processing of pain-related information as well as their cognitive, affective and behavioral response pattern when experiencing pain in daily life has been shown to be associated with poorer prognosis in low back pain. However, the relationship between specific cognitive processes such as recall of pain-related material and individual pain responses remains unknown. The present study sought to investigate recall bias in patients with chronic low back pain (CLBP) compared to healthy controls. Furthermore, it was aimed to investigate the impact of patients' individual pain-related responses on recall bias, comparing fear-avoidance response (FAR), endurance response (ER) and adaptive response (AR) patterns. Thirty-one CLBP patients and 31 controls were tested on a free recall task with three word lists comprising pain words and neutral words. Further, the CLBP group was classified into patients with a FAR, ER and AR pattern, using a short screening including the Avoidance-Endurance Questionnaire (AEQ). Group differences with pain status (CLBP vs. healthy) and AEQ responses (FAR, ER, AR) as between-group factors, word type (pain vs. neutral) as within-group factor and free recall as dependent variable were analysed by means of repeated-measures analysis of (co-) variance. Results revealed different pain processing of pain words between FAR and ER patterns, whereas CLBP patients as a whole did not differ from the healthy controls. FAR patients displayed significantly less recall than ER patients. Recall biases in CLBP patients are not only a result of experiencing pain but also effected by patients' pain response pattern with respect to fear-avoidance versus endurance.

The role of purinergic and dopaminergic systems on MK-801-induced antidepressant effects in zebrafish

Depression is a serious disease characterized by low mood, anhedonia, loss of interest in daily activities, appetite and sleep disturbances, reduced concentration, and psychomotor agitation. There is a growing interest in NMDA antagonists as a promising target for the development of new antidepressants. Considering that purinergic and dopaminergic systems are involved in depression and anxiety states, we characterized the role of these signaling pathways on MK-801-induced antidepressant effects in zebrafish. Animals treated with MK-801 at the doses of 5, 10, 15, or 20μM during 15, 30, or 60min spent longer time in the top area of aquariums in comparison to control group, indicating an anxiolytic/antidepressant effect induced by this drug. Animals treated with MK-801 spent longer time period at top area until 2 (5μM MK-801) and 4 (20μM MK-801) hours after treatment, returning to basal levels from 24h to 7days after exposure. Repeated MK-801 treatment did not induce cumulative effects, since animals treated daily during 7days had the same behavioral response pattern observed since the first until the 7th day. In order to investigate the effects of adenosine A1 and A2A receptor antagonist and agonist and the influence of modulation of adenosine levels on MK-801 effects, we treated zebrafish with caffeine, DPCPX, CPA, ZM 241385, CGS 21680, AMPCP, EHNA, dipyridamole, and NBTI during 30min before MK-801 exposure. The non-specific adenosine receptor antagonist caffeine (50mg/kg) and the selective A1 receptor antagonist DPCPX (15mg/kg) prevented the behavioral changes induced by MK-801. The non-specific nucleoside transporter (NT) inhibitor dipyridamole (10mg/kg) exacerbated the behavioral changes induced by MK-801. Dopamine receptor antagonists (sulpiride and SCH 23390) did not change the behavioral alterations induced by MK-801. Our findings demonstrated that antidepressant-like effects of MK-801 in zebrafish are mediated through adenosine A1 receptor activation.

Amygdala lesions do not compromise the cortical network for false-belief reasoning

The amygdala plays an integral role in human social cognition and behavior, with clear links to emotion recognition, trust judgments, anthropomorphization, and psychiatric disorders ranging from social phobia to autism. A central feature of human social cognition is a theory-of-mind (ToM) that enables the representation other people's mental states as distinct from one's own. Numerous neuroimaging studies of the best studied use of ToM--false-belief reasoning--suggest that it relies on a specific cortical network; moreover, the amygdala is structurally and functionally connected with many components of this cortical network. It remains unknown whether the cortical implementation of any form of ToM depends on amygdala function. Here we investigated this question directly by conducting functional MRI on two patients with rare bilateral amygdala lesions while they performed a neuroimaging protocol standardized for measuring cortical activity associated with false-belief reasoning. We compared patient responses with those of two healthy comparison groups that included 480 adults. Based on both univariate and multivariate comparisons, neither patient showed any evidence of atypical cortical activity or any evidence of atypical behavioral performance; moreover, this pattern of typical cortical and behavioral response was replicated for both patients in a follow-up session. These findings argue that the amygdala is not necessary for the cortical implementation of ToM in adulthood and suggest a reevaluation of the role of the amygdala and its cortical interactions in human social cognition.

Toxicological assessments of rats exposed prenatally to inhaled vapors of gasoline and gasoline–ethanol blends

The primary alternative to petroleum-based fuels is ethanol, which may be blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol and the lack of information about the neurodevelopmental toxicity of ethanol-blended fuels prompted the present work. Pregnant Long–Evans rats were exposed for 6.5h/day on days 9–20 of gestation to clean air or vapors of gasoline containing no ethanol (E0) or gasoline blended with 15% ethanol (E15) or 85% ethanol (E85) at nominal concentrations of 3000, 6000, or 9000ppm. Estimated maternal peak blood ethanol concentrations were less than 5mg/dL for all exposures. No overt toxicity in the dams was observed, although pregnant dams exposed to 9000ppm of E0 or E85 gained more weight per gram of food consumed during the 12days of exposure than did controls. Fuel vapors did not affect litter size or weight, or postnatal weight gain in the offspring. Tests of motor activity and a functional observational battery (FOB) administered to the offspring between post-natal day (PND) 27–29 and PND 56–63 revealed an increase in vertical activity counts in the 3000- and 9000-ppm groups in the E85 experiment on PND 63 and a few small changes in sensorimotor responses in the FOB that were not monotonically related to exposure concentration in any experiment. Neither cell-mediated nor humoral immunity were affected in a concentration-related manner by exposure to any of the vapors in 6-week-old male or female offspring. Systematic concentration-related differences in systolic blood pressure were not observed in rats tested at 3 and 6months of age in any experiment. No systematic differences were observed in serum glucose or glycated hemoglobin A1c (a marker of long-term glucose homeostasis). These observations suggest a LOEL of 3000ppm of E85 for vertical activity, LOELs of 9000ppm of E0 and E85 for maternal food consumption, and NOELs of 9000ppm for the other endpoints reported here. The ethanol content of the vapors did not consistently alter the pattern of behavioral, immunological, or physiological responses to the fuel vapors. The concentrations of the vapors used here exceed by 4–6 orders of magnitude typical exposure levels encountered by the public.

The control of automatic imitation based on bottom-up and top-down cues to animacy: insights from brain and behavior.

Humans automatically imitate other people's actions during social interactions, building rapport and social closeness in the process. Although the behavioral consequences and neural correlates of imitation have been studied extensively, little is known about the neural mechanisms that control imitative tendencies. For example, the degree to which an agent is perceived as human-like influences automatic imitation, but it is not known how perception of animacy influences brain circuits that control imitation. In the current fMRI study, we examined how the perception and belief of animacy influence the control of automatic imitation. Using an imitation-inhibition paradigm that involves suppressing the tendency to imitate an observed action, we manipulated both bottom-up (visual input) and top-down (belief) cues to animacy. Results show divergent patterns of behavioral and neural responses. Behavioral analyses show that automatic imitation is equivalent when one or both cues to animacy are present but reduces when both are absent. By contrast, right TPJ showed sensitivity to the presence of both animacy cues. Thus, we demonstrate that right TPJ is biologically tuned to control imitative tendencies when the observed agent both looks like and is believed to be human. The results suggest that right TPJ may be involved in a specialized capacity to control automatic imitation of human agents, rather than a universal process of conflict management, which would be more consistent with generalist theories of imitative control. Evidence for specialized neural circuitry that "controls" imitation offers new insight into developmental disorders that involve atypical processing of social information, such as autism spectrum disorders.