Raised Middle-Finger: Electrocortical Correlates of Social Conditioning with Nonverbal Affective Gestures

Humans form impressions of others by associating persons (faces) with negative or positive social outcomes. This learning process has been referred to as social conditioning. In everyday life, affective nonverbal gestures may constitute important social signals cueing threat or safety, which therefore may support aforementioned learning processes. In conventional aversive conditioning, studies using electroencephalography to investigate visuocortical processing of visual stimuli paired with danger cues such as aversive noise have demonstrated facilitated processing and enhanced sensory gain in visual cortex. The present study aimed at extending this line of research to the field of social conditioning by pairing neutral face stimuli with affective nonverbal gestures. To this end, electro-cortical processing of faces serving as different conditioned stimuli was investigated in a differential social conditioning paradigm. Behavioral ratings and visually evoked steady-state potentials (ssVEP) were recorded in twenty healthy human participants, who underwent a differential conditioning procedure in which three neutral faces were paired with pictures of negative (raised middle finger), neutral (pointing), or positive (thumbs-up) gestures. As expected, faces associated with the aversive hand gesture (raised middle finger) elicited larger ssVEP amplitudes during conditioning. Moreover, theses faces were rated as to be more arousing and unpleasant. These results suggest that cortical engagement in response to faces aversively conditioned with nonverbal gestures is facilitated in order to establish persistent vigilance for social threat-related cues. This form of social conditioning allows to establish a predictive relationship between social stimuli and motivationally relevant outcomes.     

Regional brain metabolic activation during craving elicited by recall of previous drug experiences

Cocaine cues elicit craving and physiological responses. The cerebral circuits involved in these are poorly understood. The purpose of this study was to assess the relation between regional brain activation and cocaine cue elicited responses. Thirteen right-handed cocaine abusers were scanned with positron emission tomography (PET) and [F-18] fluorodeoxyglucose (FDG) twice; during an interactive interview about neutral themes and during an interactive interview about cocaine themes designed to elicit cocaine craving. In parallel the behavioral (rated from 0: felt nothing to 10: felt extreme) and cardiovascular responses were recorded. During the cocaine theme interview subjects reported higher self reports for cocaine craving (+2.5+/-3.3, p < or = 0.02) and had higher heart rates (+4.7+/-7.2%, p < or = 0.001), systolic (+4+/-4%, p < or = 0.0001), and diastolic blood pressures (+2.6+/-3.8%, p < or = 0.003) than during the neutral interview. Absolute and relative metabolic values in the orbitofrontal (+16.4+/-17.1%, p < or = 0.005; +11.3+/-14.3%, p < or = 0.008) and left insular cortex (+21.6+/-19.6%, p < or = 0.002; +16.7+/-19.7%, p < or = 0.01) and relative values in cerebellum (+17.9+/-14.8%, p < or = 0.0008) were higher during the cocaine theme than during the neutral theme interview. Relative metabolic values in the right insular region (p < or = 0.0008) were significantly correlated with self reports of cocaine craving. Activation of the temporal insula, a brain region involved with autonomic control, and of the orbitofrontal cortex, a brain region involved with expectancy and reinforcing salience of stimuli, during the cocaine theme support their involvement with craving in cocaine addicted subjects.     

Kinase interest you in treating incubated cocaine‐craving? A hypothetical model for treatment intervention during protracted withdrawal from cocaine

A diagnostic criterion for drug addiction, persistent drug‐craving continues to be the most treatment‐resistant aspect of addiction that maintains the chronic, relapsing, nature of this disease. Despite the high prevalence of psychomotor stimulant addiction, there currently exists no FDA‐approved medication for craving reduction. In good part, this reflects our lack of understanding of the neurobiological underpinnings of drug‐craving. In humans, cue‐elicited drug‐craving is associated with the hyperexcitability of prefrontal cortical regions. Rodent models of cocaine addiction indicate that a history of excessive cocaine‐taking impacts excitatory glutamate signaling within the prefrontal cortex to drive drug‐seeking behavior during protracted withdrawal. This review summarizes evidence that the capacity of cocaine‐associated cues to augment craving in highly drug‐experienced rats relates to a withdrawal‐dependent incubation of glutamate release within prelimbic cortex. We discuss how stimulation of mGlu1/5 receptors increases the activational state of both canonical and noncanonical intracellular signaling pathways and present a theoretical molecular model in which the activation of several kinase effectors, including protein kinase C, extracellular signal‐regulated kinase and phosphoinositide 3‐kinase (PI3K) might lead to receptor desensitization to account for persistent cocaine‐craving during protracted withdrawal. Finally, this review discusses the potential for existing, FDA‐approved, pharmacotherapeutic agents that target kinase function as a novel approach to craving intervention in cocaine addiction.     

Classical conditioning, decay and extinction of cocaine-induced hyperactivity and stereotypy

Following 10 daily pairings of multiple conditioned stimuli with injection of cocaine (15 mg/kg), the presentation of the stimuli alone elicited behaviors in rats similar to those induced by cocaine. The behaviors included increased duration or frequency of rearing, sniffing, head bobbing, and horizontal locomotor activity (crossing). The level of the conditioned response for several of these behaviors approximated that induced by the drug itself. The conditioned drug effect showed decay over 15 days but little extinction during 4 daily trials. Brain concentrations of the dopamine metabolites, homovanillic acid and dihydroxyphenylacetic acid, were similar in the conditioned and pseudoconditioned control groups in both the caudate and mesolimbic areas. The behavioral results demonstrate that, in a classical conditioning paradigm, previously neutral stimuli can elicit behaviors similar to those induced by cocaine and that certain conditioned responses show time related decline. This agrees with the reported conditioning of amphetamine's behavioral effects but differs in terms of the action on brain dopamine turnover.     

Cue-reactors: individual differences in cue-induced craving after food or smoking abstinence

Background

Pavlovian conditioning plays a critical role in both drug addiction and binge eating. Recent animal research suggests that certain individuals are highly sensitive to conditioned cues, whether they signal food or drugs. Are certain humans also more reactive to both food and drug cues?

Methods

We examined cue-induced craving for both cigarettes and food, in the same individuals (n = 15 adult smokers). Subjects viewed smoking-related or food-related images after abstaining from either smoking or eating.

Results

Certain individuals reported strong cue-induced craving after both smoking and food cues. That is, subjects who reported strong cue-induced craving for cigarettes also rated stronger cue-induced food craving.

Conclusions

In humans, like in nonhumans, there may be a “cue-reactive” phenotype, consisting of individuals who are highly sensitive to conditioned stimuli. This finding extends recent reports from nonhuman studies. Further understanding this subgroup of smokers may allow clinicians to individually tailor therapies for smoking cessation.     

The influence of serotonin on fear learning

Learning of associations between aversive stimuli and predictive cues is the basis of Pavlovian fear conditioning and is driven by a mismatch between expectation and outcome. To investigate whether serotonin modulates the formation of such aversive cue-outcome associations, we used functional magnetic resonance imaging (fMRI) and dietary tryptophan depletion to reduce brain serotonin (5-HT) levels in healthy human subjects. In a Pavlovian fear conditioning paradigm, 5-HT depleted subjects compared to a non-depleted control group exhibited attenuated autonomic responses to cues indicating the upcoming of an aversive event. These results were closely paralleled by reduced aversive learning signals in the amygdala and the orbitofrontal cortex, two prominent structures of the neural fear circuit. In agreement with current theories of serotonin as a motivational opponent system to dopamine in fear learning, our data provide first empirical evidence for a role of serotonin in representing formally derived learning signals for aversive events.     

Nucleus accumbens neurons are innately tuned for rewarding and aversive taste stimuli, encode their predictors, and are linked to motor output

The nucleus accumbens (NAc) is a key component of the brain's reward pathway, yet little is known of how NAc cells respond to primary rewarding or aversive stimuli. Here, naive rats received brief intraoral infusions of sucrose and quinine paired with cues in a classical conditioning paradigm while the electrophysiological activity of individual NAc neurons was recorded. NAc neurons (102) were typically inhibited by sucrose (39 of 52, 75%) or excited by quinine (30 of 40, 75%) infusions. Changes in firing rate were correlated with the oromotor response to intraoral infusions. Most taste-responsive neurons responded to only one of the stimuli. NAc neurons developed responses to the cues paired with sucrose and quinine. Thus, NAc neurons are innately tuned to rewarding and aversive stimuli and rapidly develop responses to predictive cues. The results indicate that the output of the NAc is very different when rats taste rewarding versus aversive stimuli.     

The Influence of Learning on Host Plant Preference in a Significant Phytopathogen Vector,Diaphorina citri

Although specialist herbivorous insects are guided by innate responses to host plant cues, host plant preference may be influenced by experience and is not dictated by instinct alone. The effect of learning on host plant preference was examined in the Asian citrus psyllid, Diaphorina citri; vector of the causal agent of citrus greening disease or huanglongbing. We investigated: a) whether development on specific host plant species influenced host plant preference in mature D. citri; and b) the extent of associative learning in D. citri in the form of simple and compound conditioning. Learning was measured by cue selection in a 2-choice behavioral assay and compared to naïve controls. Our results showed that learned responses in D. citri are complex and diverse. The developmental host plant species influenced adult host plant preference, with female psyllids preferring the species on which they were reared. However, such preferences were subject to change with the introduction of an alternative host plant within 24–48 hrs, indicating a large degree of experience-dependent response plasticity. Additionally, learning occurred for multiple sensory modalities where novel olfactory and visual environmental cues were associated with the host plant. However, males and females displayed differing discriminatory abilities. In compound conditioning tasks, males exhibited recognition of a compound stimulus alone while females were capable of learning the individual components. These findings suggest D. citri are dynamic animals that demonstrate host plant preference based on developmental and adult experience and can learn to recognize olfactory and visual host plant stimuli in ways that may be sex specific. These experience-based associations are likely used by adults to locate and select suitable host plants for feeding and reproduction and may suggest the need for more tailored lures and traps, which reflect region-specific cultivars or predominate Rutaceae in the area being monitored.     

Extinction of cocaine self-administration reveals functionally and temporally distinct dopaminergic signals in the nucleus accumbens

While Pavlovian and operant conditioning influence drug-seeking behavior, the role of rapid dopamine signaling in modulating these processes is unknown. During self-administration of cocaine, two dopaminergic signals, measured with 100 ms resolution, occurred immediately before and after the lever press (termed pre- and post-response dopamine transients). Extinction of self-administration revealed that these two signals were functionally distinct. Pre-response transients, which could reflect the motivation to obtain the drug, did not decline during extinction. Remarkably, post-response dopamine transients attenuated as extinction progressed, suggesting that they encode the learned association between environmental cues and cocaine. A third type of dopamine transient, not time locked to overt stimuli, decreased in frequency during extinction and correlated with calculated cocaine concentrations. These results show that dopamine release transients involved in different aspects of cocaine self-administration are highly plastic--differentially governed by motivation, learned associations linked with environmental stimuli, and the pharmacological actions of cocaine.     

Functional specialization of mouse higher visual cortical areas

The mouse is emerging as an important model for understanding how sensory neocortex extracts cues to guide behavior, yet little is known about how these cues are processed beyond primary cortical areas. Here, we used two-photon calcium imaging in awake mice to compare visual responses in primary visual cortex (V1) and in two downstream target areas, AL and PM. Neighboring V1 neurons had diverse stimulus preferences spanning five octaves in spatial and temporal frequency. By contrast, AL and PM neurons responded best to distinct ranges of stimulus parameters. Most strikingly, AL neurons preferred fast-moving stimuli while PM neurons preferred slow-moving stimuli. By contrast, neurons in V1, AL, and PM demonstrated similar selectivity for stimulus orientation but not for stimulus direction. Based on these findings, we predict that area AL helps guide behaviors involving fast-moving stimuli (e.g., optic flow), while area PM?helps guide behaviors involving slow-moving objects.     

Induction of immediate early genes in the mouse auditory cortex after auditory cued fear conditioning to complex sounds

Immediate early genes (IEGs) are widely used as markers to delineate neuronal circuits because they show fast and transient expression induced by various behavioral paradigms. In this study, we investigated the expression of the IEGs c-fos and Arc in the auditory cortex of the mouse after auditory cued fear conditioning using quantitative polymerase chain reaction and microarray analysis. To test for the specificity of the IEG induction, we included several control groups that allowed us to test for factors other than associative learning to sounds that could lead to an induction of IEGs. We found that both c-fos and Arc showed strong and robust induction after auditory fear conditioning. However, we also observed increased expression of both genes in any control paradigm that involved shocks, even when no sounds were presented. Using mRNA microarrays and comparing the effect of the various behavioral paradigms on mRNA expression levels, we did not find genes being selectively upregulated in the auditory fear conditioned group. In summary, our results indicate that the use of IEGs to identify neuronal circuits involved specifically in processing of sound cues in the fear conditioning paradigm can be limited by the effects of the aversive unconditional stimulus and that activity levels in a particular primary sensory cortical area can be strongly influenced by stimuli mediated by other modalities.     

Local non-linear interactions in the visual cortex may reflect global decorrelation

The classical receptive field in the primary visual cortex have been successfully explained by sparse activation of relatively independent units, whose tuning properties reflect the statistical dependencies in the natural environment. Robust surround modulation, emerging from stimulation beyond the classical receptive field, has been associated with increase of lifetime sparseness in the V1, but the system-wide modulation of response strength have currently no theoretical explanation. We measured fMRI responses from human visual cortex and quantified the contextual modulation with a decorrelation coefficient (d), derived from a subtractive normalization model. All active cortical areas demonstrated local non-linear summation of responses, which were in line with hypothesis of global decorrelation of voxels responses. In addition, we found sensitivity to surrounding stimulus structure across the ventral stream, and large-scale sensitivity to the number of simultaneous objects. Response sparseness across voxel population increased consistently with larger stimuli. These data suggest that contextual modulation for a stimulus event reflect optimization of the code and perhaps increase in energy efficiency throughout the ventral stream hierarchy. Our model provides a novel prediction that average suppression of response amplitude for simultaneous stimuli across the cortical network is a monotonic function of similarity of response strengths in the network when the stimuli are presented alone.     

Contextual taste cues modulate olfactory learning in C. elegans by an occasion-setting mechanism

Manipulations of context can affect learning and memory performance across species in many associative learning paradigms. Using taste cues to create distinct contexts for olfactory adaptation assays in the nematode Caenorhabditis elegans, we now show that performance in this associative learning paradigm is sensitive to context manipulations, and we investigate the mechanism(s) used for the integration of context cues in learning. One possibility is that the taste and olfactory stimuli are perceived as a combined, blended cue that the animals then associate with the unconditioned stimulus (US) in the same manner as with any other unitary conditioned stimuli (CS). Alternatively, an occasion-setting model suggests that the taste cues only define the appropriate context for olfactory memory retrieval without directly entering into the primary association. Analysis of genetic mutants demonstrated that the olfactory and context cues are sensed by distinct primary sensory neurons and that the animals' ability to use taste cues to modulate olfactory learning is independent from their ability to utilize these same taste cues for adaptation. We interpret these results as evidence for the occasion-setting mechanism in which context cues modulate primary Pavlovian association by functioning in a hierarchical manner to define the appropriate setting for memory recall.     

The Value of Artificial Stimuli in Behavioral Research: Making the Case for Egg Rejection Studies in Avian Brood Parasitism

Experimentation is at the heart of classical and modern behavioral ecology research. The manipulation of natural cues allows us to establish causation between aspects of the environment, both internal and external to organisms, and their effects on animals' behaviors. In recognition systems research, including the quest to understand the coevolution of sensory cues and decision rules underlying the rejection of foreign eggs by hosts of avian brood parasites, artificial stimuli have been used extensively, but not without controversy. In response to repeated criticism about the value of artificial stimuli, we describe four potential benefits of using them in egg recognition research, two each at the proximate and ultimate levels of analysis: (1) the standardization of stimuli for developmental studies and (2) the disassociation of correlated traits of egg phenotypes used for sensory discrimination, as well as (3) the estimation of the strength of selection on parasitic egg mimicry and (4) the establishment of the evolved limits of sensory and cognitive plasticity. We also highlight constraints of the artificial stimulus approach and provide a specific test of whether responses to artificial cues can accurately predict responses to natural cues. Artificial stimuli have a general value in ethological research beyond research in brood parasitism and may be especially critical in field studies involving the manipulation of a single parameter, where other, confounding variables are difficult or impossible to control experimentally or statistically.     

Spinal reflexes in the long-tailed stingray, Himantura fai

We have exploited the segregation of motor and sensory axons into peripheral nerve sub-compartments to examine spinal reflex interactions in anaesthetized stingrays. Single, supra-maximal electrical stimuli delivered to segmental sensory nerves elicited compound action potentials in the motor nerves of the stimulated segment and in rostral and caudal segmental motor nerves. Compound action potentials elicited in segmental motor nerves by single stimuli delivered to sensory nerves were increased severalfold by prior stimulation of adjacent sensory nerves. This facilitation of the segmental reflex produced by intense conditioning stimuli decreased as it was applied to more remote segments, to approximately the same degree in up to seven segments in the rostral and caudal direction. In contrast, an asymmetric response was revealed when test and conditioning stimuli were delivered to different nerves, neither of which was of the same segment as the recorded motor nerve: in this configuration, conditioning volleys generally inhibited the responses of motoneurons to stimuli delivered to more caudally located sensory nerves. This suggests that circuitry subserving trans-segmental interactions between spinal afferents is present in stingrays and that interneuronal connections attenuate the influence that subsequent activity in caudal primary afferents can have on the motor elements.     

Social facilitation of insect reproduction with motor-driven tactile stimuli

Tactile stimuli provide animals with important information about the environment, including physical features such as obstacles, and biologically relevant cues related to food, mates, hosts and predators. The antennae, the principal sensory organs of insects, house an array of sensory receptors for olfaction, gustation, audition, nociception, balance, stability, graviception, static electric fields, and thermo-, hygro- and mechanoreception. The antennae, being the anteriormost sensory appendages, play a prominent role in social interactions with conspecifics that involve primarily chemosensory and tactile stimuli. In the German cockroach (Blattella germanica) antennal contact during social interactions modulates brain-regulated juvenile hormone production, ultimately accelerating the reproductive rate in females. The primary sensory modality mediating this social facilitation of reproduction is antennal mechanoreception. We investigated the key elements, or stimulus features, of antennal contact that socially facilitate reproduction in B. germanica females. Using motor-driven antenna mimics, we assessed the physiological responses of females to artificial tactile stimulation. Our results indicate that tactile stimulation with artificial materials, some deviating significantly from the native antennal morphology, can facilitate female reproduction. However, none of the artificial stimuli matched the effects of social interactions with a conspecific female.     

Neural Responses to Smoking Stimuli Are Influenced by Smokers' Attitudes towards Their Own Smoking Behaviour

An important feature of addiction is the high drug craving that may promote the continuation of consumption. Environmental stimuli classically conditioned to drug-intake have a strong motivational power for addicts and can elicit craving. However, addicts differ in the attitudes towards their own consumption behavior: some are content with drug taking (consonant users) whereas others are discontent (dissonant users). Such differences may be important for clinical practice because the experience of dissonance might enhance the likelihood to consider treatment. This fMRI study investigated in smokers whether these different attitudes influence subjective and neural responses to smoking stimuli. Based on self-characterization, smokers were divided into consonant and dissonant smokers. These two groups were presented smoking stimuli and neutral stimuli. Former studies have suggested differences in the impact of smoking stimuli depending on the temporal stage of the smoking ritual they are associated with. Therefore, we used stimuli associated with the beginning (BEGIN-smoking-stimuli) and stimuli associated with the terminal stage (END-smoking-stimuli) of the smoking ritual as distinct stimulus categories. Stimulus ratings did not differ between both groups. Brain data showed that BEGIN-smoking-stimuli led to enhanced mesolimbic responses (amygdala, hippocampus, insula) in dissonant compared to consonant smokers. In response to END-smoking-stimuli, dissonant smokers showed reduced mesocortical responses (orbitofrontal cortex, subcallosal cortex) compared to consonant smokers. These results suggest that smoking stimuli with a high incentive value (BEGIN-smoking-stimuli) are more appetitive for dissonant than consonant smokers at least on the neural level. To the contrary, smoking stimuli with low incentive value (END-smoking-stimuli) seem to be less appetitive for dissonant smokers than consonant smokers. These differences might be one reason why dissonant smokers experience difficulties in translating their attitudes into an actual behavior change.     

How rats combine temporal cues

The procedures for classical and operant conditioning, and for many timing procedures, involve the delivery of reinforcers that may be related to the time of previous reinforcers and responses, and to the time of onsets and terminations of stimuli. The behavior resulting from such procedures can be described as bouts of responding that occur in some pattern at some rate. A packet theory of timing and conditioning is described that accounts for such behavior under a wide range of procedures. Applications include the food searching by rats in Skinner boxes under conditions of fixed and random reinforcement, brief and sustained stimuli, and several response-food contingencies. The approach is used to describe how multiple cues from reinforcers and stimuli combine to determine the rate and pattern of response bouts.