Role of the motor cortex in the generation of classically conditioned eyelid and vibrissae responses

The eyelid motor system has been used for years as an experimental model for studying the neuronal mechanisms underlying motor and cognitive learning, mainly with classical conditioning procedures. Nonetheless, it is not known yet which brain structures, or neuronal mechanisms, are responsible for the acquisition, storage, and expression of these motor responses. Here, we studied the temporal correlation between unitary activities of identified eyelid and vibrissae motor cortex neurons and the electromyographic activity of the orbicularis oculi and vibrissae muscles and magnetically recorded eyelid positions during classical conditioning of eyelid and vibrissae responses, using both delay and trace conditioning paradigms in behaving mice. We also studied the involvement of motor cortex neurons in reflexively evoked eyelid responses and the kinematics and oscillatory properties of eyelid movements evoked by motor cortex microstimulation. Results show the involvement of the motor cortex in the performance of conditioned responses elicited during the classical conditioning task. However, a timing correlation analysis showed that both electromyographic activities preceded the firing of motor cortex neurons, which must therefore be related more with the reinforcement and/or proper performance of the conditioned responses than with their acquisition and storage.

Pain after Psychological Trauma: The Role of Classical Conditioning

Psychological trauma is typically accompanied by physical pain, and posttraumatic stress disorder (PTSD) often co-occurs with chronic pain. Clinical reports suggest that pain in the aftermath of trauma may be part of a re-experiencing symptomatology. Previously, we demonstrated that classical conditioning can underlie visual re-experiencing since intrusions appear to occur as conditioned responses (CRs) to trauma-related cues. Possibly, classical conditioning also plays a role in re-experiencing of pain. However, this hypothesis has so far remained untested. Sixty-five participants underwent classical conditioning, where painful electrical stimulation and highly aversive film-clips served as unconditioned stimuli (USs) in a 2 (pain/no pain) x 2 (aversive/neutral film) design. Conditioned stimuli (CSs) were neutral pictures depicting contextual details from the films. One day later, participants were re-exposed to CSs during a memory-triggering-task (MTT). Pain-CRs were assessed by self-report and an fMRI-based marker of nociceptive pain, the neurologic pain signature (NPS).During conditioning, pain-signaling CSs elicited more self-reported pain and NPS responses than no-pain-signaling CSs. Self-reported pain-CRs but not NPS CRs recurred 24h later when participants were re-exposed to CSs during MTT. Both during acquisition and MTT, the aversive affective film-context blurred the difference in participants´ pain-reports to pain-signaling and no-pain-signaling CSs.Our data support the hypothesis that pain can emerge as a classically conditioned response. Pain as a CR to pain-signaling cues could represent an instance of pain re-experiencing in PTSD. Possibly, this mechanism may perpetuate pain beyond tissue healing and thereby explain the comorbidity between chronic pain and PTSD.

Effects of oxytocin administration and conditioned oxytocin on brain activity: an fMRI study.

It has been demonstrated that secretion of several hormones can be classically conditioned, however, the underlying brain responses of such conditioning have never been investigated before. In this study we aimed to investigate how oxytocin administration and classically conditioned oxytocin influence brain responses. In total, 88 females were allocated to one of three groups: oxytocin administration, conditioned oxytocin, or placebo, and underwent an experiment consisting of three acquisition and three evocation days. Participants in the conditioned group received 24 IU of oxytocin together with a conditioned stimulus (CS) during three acquisition days and placebo with the CS on three evocation days. The oxytocin administration group received 24 IU of oxytocin and the placebo group received placebo during all days. On the last evocation day, fMRI scanning was performed for all participants during three tasks previously shown to be affected by oxytocin: presentation of emotional faces, crying baby sounds and heat pain. Region of interest analysis revealed that there was significantly lower activation in the right amygdala and in two clusters in the left superior temporal gyrus in the oxytocin administration group compared to the placebo group in response to observing fearful faces. The activation in the conditioned oxytocin group was in between the other two groups for these significant clusters but did not significantly differ from either group. No group differences were found in the other tasks. The findings carefully suggest that a conditioned response in brain activity was observed, however the conditioned group did not significantly differ from the other groups. Future research should therefore investigate the optimal timing of conditioned endocrine responses and study whether the findings generalize to other hormones as well.

Different brain networks mediate the effects of social and conditioned expectations on pain

Information about others’ experiences can strongly influence our own feelings and decisions. But how does such social information affect the neural generation of affective experience, and are the brain mechanisms involved distinct from those that mediate other types of expectation effects? Here, we used fMRI to dissociate the brain mediators of social influence and associative learning effects on pain. Participants viewed symbolic depictions of other participants’ pain ratings (social information) and classically conditioned pain-predictive cues before experiencing painful heat. Social information and conditioned stimuli each had significant effects on pain ratings, and both effects were mediated by self-reported expectations. Yet, these effects were mediated by largely separable brain activity patterns, involving different large-scale functional networks. These results show that learned versus socially instructed expectations modulate pain via partially different mechanisms—a distinction that should be accounted for by theories of predictive coding and related top-down influences.

Mindfulness Training Disrupts Pavlovian Conditioning

Classical conditioning is a quintessential learning process; however, maladaptive forms of conditioning sustain many unhealthy behaviors (e.g., addiction). Mindfulness training is theorized to de-automatize conditioned behavior by decoupling stimulus and response. This study assessed the effect of mindfulness training on conditioned behavior during a classical conditioning task. Findings indicated mindfulness training decreased classically conditioned behavior relative to an active control condition, delaying the onset of first conditioned response and decreasing conditioned response frequency. Thus, mindfulness training may be one method of increasing volitional control over maladaptive conditioned behaviors that contribute to the development and maintenance of clinical disorders.

Development of Pavlovian-to-instrumental transfer (PIT) task to examine the effects of reward-predicting cues on behavioral activation in young adults

There is a growing recognition that much of human behavior is governed by the presence of classically conditioned cues. The Pavlovian-to-Instrumental Transfer (PIT) paradigm offers a way to measure the effects of classically conditioned stimuli on behavior. In the current study, a novel PIT paradigm was developed for use in conjunction with an fMRI classical conditioning task. This could allow for a measurement of BOLD responses to anticipated rewards, unconfounded by operant responses, while providing a behavioral measure of conditioning effects. Twenty-four healthy young adults completed 1) instrumental training, 2) Pavlovian conditioning, and 3) Transfer test. During instrumental training, participants learned to apply force on a handgrip to win money from slot machines pictured on a computer screen. During Pavlovian conditioning, slot machines appeared with one of two abstract symbols (cues), one symbol was predictive of monetary reward. During the Transfer test, participants again applied force on a handgrip to win more money. This time, slot machines were presented with the Pavlovian cues, but with the outcomes hidden. The results indicated increased effort on the instrumental task, i.e., higher response frequency and greater force, in the presence of a reward-predicting cue. Our findings add to a growing number of studies demonstrating PIT effects in humans. This paradigm was proved to be useful in measuring the effects of a conditioned stimulus on behavioral activation.