Classical Eyelid Conditioning Research Articles

Classical eyelid conditioning, psychopathy, and Hans Eysenck's grand theory

The concept of conditionability, usually assessed in classical preparations such as the eyelid conditioning paradigm, was one of the original cornerstones of Eysenck's goal for a grand theory moving seamlessly from biology (inherited and acquired CNS differences), through basic learning, to personality, and to clinical syndromes, including psychopathy and criminal conduct. From a somewhat personal perspective we trace the beginning of classical conditioning research in Eysenck's research programme at the Institute of Psychiatry (Maudsley Hospital), through various technical developments, which eventually led to questions regarding the adequacy of the construct of conditionability itself. Nevertheless, contemporary research on psychopathy, drawing on new approaches to personality theory and sub-types of psychopathic individuals, is still influenced by Eysenck's interest in crime and personality. While most of the details of the original model have been challenged, there is still a surprising consonance between Eysenck's theory and modern approaches to research on the nature of psychopathy. Conditioning studies of psychopathic individuals could still benefit further from insights developed in Eysenck's laboratories.

Prolonging the postcomplex spike pause speeds eyeblink conditioning

Climbing fiber input to the cerebellum is believed to serve as a teaching signal during associative, cerebellum-dependent forms of motor learning. However, it is not understood how this neural pathway coordinates changes in cerebellar circuitry during learning. Here, we use pharmacological manipulations to prolong the postcomplex spike pause, a component of the climbing fiber signal in Purkinje neurons, and show that these manipulations enhance the rate of learning in classical eyelid conditioning. Our findings elucidate an unappreciated aspect of the climbing fiber teaching signal, and are consistent with a model in which convergent postcomplex spike pauses drive learning-related plasticity in the deep cerebellar nucleus. They also suggest a physiological mechanism that could modulate motor learning rates.

Conditioned Eyelid Movement Is not a Blink

Based on kinematic properties and distinct substrates, there are different classes of eyelid movement described as eyeblinks. We investigate whether the eyelid movements made in response to a conditioned stimulus (CS) are a category of eyelid movements distinct from blinks. Human subjects received 60 trials of classical eyelid conditioning with a tone as the CS and electrical stimulation of the supraorbital branch of the trigeminal nerve as the unconditioned stimulus (UCS). Before and after training, reflex blinks were elicited with the UCS. The kinematics of conditioned responses (CRs) differed significantly from those of reflex blinks. The slope of the amplitude-maximum velocity function was steeper for reflex blinks than for CRs, and reflex blink duration was significantly shorter than CR duration. Unlike reflex blinks, for which maximum velocity was independent of blink duration, the maximum velocity of CRs depended on CR duration. These quantitative and qualitative differences indicated that CRs were a unique class of eyelid movements distinct from blinks and eyelid movements with vertical saccadic gaze shifts.

Changes in Rabbit Cerebellar Cortical and Interpositus Nucleus Activity during Acquisition, Extinction, and Backward Classical Eyelid Conditioning

Multiple- and single-unit neuronal activities were recorded from cerebellar cortex (Larsell's lobule HVI and adjacent ansiform cortex) and the cerebellar interpositus nucleus during forward (CS-US), backward (US-CS), and explicitly unpaired classical eyeblink conditioning in several rabbits. Whereas learning-related activity was observed in the interpositus nucleus only during forward pairing of the conditioning stimuli, a variety of patterns of learning-related neuronal firings were observed in cerebellar cortex during forward, backward, and even unpaired presentations of the conditioning stimuli. These data suggest that the cerebellar cortex and the deep cerebellar nuclei play different roles during classical eyeblink conditioning.

How long do relational representations in the hippocampus last during classical eyelid conditioning?

How long do relational representations in the hippocampus last during classical eyelid conditioning?

Multiple-unit activity from rabbit cerebellar cortex and interpositus nucleus during classical discrimination/reversal eyelid conditioning

Multiple-unit activity was monitored in the hemispheric lobule VI (HVI) and the interpositus nucleus of the cerebellum during classical discrimination and reversal eyelid conditioning in rabbits. During both phases of conditioning similar patterns of activity were observed in lobule HVI: conditioned response (CR)-related activity was present on conditioned stimulus (CS)+ trials but not on CS — trials. Activity in the interpositus nucleus differed during the two phases of conditioning. After discrimination training, CR-related activity was present on CS + but not CS— trials. After reversal training, however, only a weak activation of the interpositus nucleus was seen on CS + trials with no activation present on CS — trials. These data suggest that lobule HVI and the interpositus nucleus may play different roles in classical eyelid conditioning.

Neuronal activity in rabbit neostriatum during classical eyelid conditioning.

Extracellular multiple- and single-unit recordings were made from the neostriatum of rabbits during classical eyelid conditioning. Neostriatal neurons processed information regarding the conditioned auditory stimulus (CS) and conditioned eyelid response (CR) as well as the unconditioned stimulus/response (US/UR). These data are consistent with previous reports that neostriatal neurons respond to movement and movement-related sensory stimuli. In most cases, neostriatal neurons increased activity to the US during the early phase of training, but to the CR as training progressed. A close temporal correlation was found between neuronal activity and CR onset with unit discharges typically preceding CR onset by 10-50 ms. The activity of some multiple and single units was monitored after injection of haloperidol, a neuroleptic and dopamine antagonist known to disrupt neostriatal function. Interestingly, haloperidol caused a greater disruption of CRs at low-intensity than at high-intensity CSs, but conditioning-related neuronal activity was disrupted equally at both intensities. These data are discussed in terms of a possible role for the neostriatum in eyelid conditioning.

Unilateral inferior olive NMDA lesion leads to unilateral deficit in acquisition and retention of eyelid classical conditioning

New Zealand White rabbits (Oryctolagus cuniculus) were trained for acquisition (N = 21) or retention (N = 10) of classical eyelid conditioning with unilateral or bilateral N-methyl-DL-aspartate chemical lesions of the rostromedial dorsal accessory inferior olive (rmDAO; multiple injections totaling 76 to 342 nmol). In all instances, subjects were unable to learn or retain conditioning on the side contralateral to the lesion. Learning rates were comparable for lesions outside of the rmDAO and sham operates. These findings demonstrate a specific unilateral deficit whereas in previous research the answer to this question was ambiguous since electrolytic lesions effectively cause bilateral olivary lesions. This research agrees with the concept that the inferior olive projects essential information about the unconditioned stimulus to a cerebellar locus of learning and memory for classical conditioning.

Possible CS and US pathways for rabbit classical eyelid conditioning: Electrophysiological evidence for projections from the pontine nuclei and inferior olive to cerebellar cortex and nuclei

Projections from the lateral region of the pontine nuclei and the dorsal accessory inferior olive to both cerebellar cortex and cerebellar dentate/interpositus nuclei were electrophysiologically examined using single-pulse stimulation and single-unit and population recording. Stimulation of the pontine nuclear region activated population potentials and single units recorded in both cerebellar cortex and deep nuclei. Pontine-evoked activity in cerebellar cortex (Larsell's lobule HVI and adjacent areas) was rather well-defined and strong while pontine-evoked activity in the deep cerebellar nuclei seemed relatively more diffuse and weaker. Short onset latencies for both single units and population potentials were found suggesting direct projections. Similar to previous studies, inferior olive stimulation evoked short-latency responses in cerebellar cortex and nuclei thus suggesting direct projections. More pontine- and olivary-evoked activity was seen in cortex than in the nuclei with slightly more olivary-evoked potentials per recording electrode penetration observed than pontine-evoked activity. Our findings suggest that cortical and nuclear regions of the cerebellum receive converging projections from the pontine nuclei and inferior olive, projections that may carry information about stimuli used during classical conditioning. These findings are discussed in terms of cerebellar circuits that may be involved in classical eyelid conditioning.

Disruption of classical eyelid conditioning after cerebellar lesions: damage to a memory trace system or a simple performance deficit?

Over the past 10 years, a number of laboratories have reported that classically conditioned skeletal muscle responses, such as conditioned nictitating membrane/eyelid responses, are critically dependent on activity in the cerebellum. For example, unilateral lesions of the cerebellar interpositus nucleus have been shown to prevent acquisition and abolish retention of the conditioned eyelid response on the side ipsilateral to the lesions without affecting conditioned responding (CR) on the contralateral side. Also, recording studies involving the interpositus nucleus have consistently revealed patterns of neuronal discharge that predict execution of the CR. The lesion and recording studies have generally been cited as evidence that plasticity in the cerebellum is critically involved in the learning and memory of classically conditioned responses. This interpretation was recently challenged by Welsh and Harvey (1989a), who claimed that cerebellar lesions simply produced a performance deficit and speculated that the role of the cerebellum was not in learning and memory processes associated with the CR but only in performance of the eye blink response. Presented here are three experiments that provide additional strong evidence for a critical role of the cerebellum in the learning and memory of the Pavlovian CR. These experiments include (1) demonstrations of complete and permanent CR abolition after appropriate interpositus lesions, (2) a failure to find systematic or persisting decrements in the unconditioned response amplitude (i.e., the eye blink reflex) after appropriate interpositus lesion, and (3) observations of differential effects on the CR and unconditioned response after lesions were placed in populations of motoneurons responsible for executing the eye blink response. These data are discussed in the context of performance versus learning issues; evidence presented here rules out the possibility that interpositus lesion abolition of the eye blink CR is simply due to lesion effects on performance.

Possible conditioned stimulus pathway for classical eyelid conditioning in rabbits. I. Anatomical evidence for direct projections from the pontine nuclei to the cerebellar interpositus nucleus

Wheat germ agglutinin and cholera toxin-conjugated horseradish peroxidase (HRP) were used to retrogradely and anterogradely trace connectivity between the lateral regions of the pontine nuclei and the anterior interpositus nucleus of the cerebellum in rabbits. Projections from the pontine nuclei were found to terminate in the anterior interpositus nucleus and the interpositus was found to send projections to the pontine nuclei. Projections from the nucleus reticularis tegmenti pontis, dorsal accessory inferior olive, and Larsell's lobule HVI of the cerebellum were also found to terminate in the interpositus nucleus and projections from the interpositus nucleus to the inferior olivary complex were observed. The projections from brain stem regions to the interpositus nucleus are discussed as possible pathways that are involved in classical eyelid conditioning.

Dorsal accessory inferior olive activity diminishes during acquisition of the rabbit classically conditioned eyelid response

Eight rabbits were implanted with chronic recording electrodes in the rostromedial region of the dorsal accessory inferior olive (DAO). Multiple-unit DAO activity was recorded during 5 training sessions consisting of paired tone conditioned stimulus (CS) and air puff unconditioned stimulus (US) trials. Initially, the air puff US produced a large somatosensory-evoked response in the DAO during the paired CS-US presentations. As percent CRs increased across sessions, however, the DAO activity on paired trials decreased dramatically. In contrast, there were no significant decreases in DAO activity on US-alone trials presented at the end of each paired conditioning session. These results suggest that an associative process suppresses DAO activity during classical eyelid conditioning. Possible mechanisms of DAO inhibition and its involvement as part of the US 'reinforcement' pathway are discussed.

Haloperidol impairs classically conditioned nictitating membrane responses and conditioning-related cerebellar interpositus nucleus activity in rabbits

Rabbits, chronically implanted with recording electrodes in the cerebellar interpositus nucleus and following acquisition of a classically conditioned eyelid response, were injected with haloperidol (HAL, 250 μg/kg). HAL significantly reduced the number of conditioned responses when a 75 and 85 dB tone conditioned stimulus (CS) was presented but not when a 95 dB tone CS was used. There was a corresponding decrease in interpositus activity at the 75 and 85 dB CS intensities but not at the 95 dB intensity. HAL appeared to disrupt CRs and interpositus activity by increasing the intensity threshold of the tone CS for eliciting conditioned responses. Possible mechanisms for the effect of HAL on neural circuitry involved in classical eyelid conditioning are discussed.

Classical discrimination conditioning of the rabbit's eyelid response using pontine stimulation as a conditioned stimulus

Classical discrimination conditioning of the nictitating membrane/eyelid response was performed on seven rabbits using stimulation of the pontine nuclei or middle cerebellar peduncle as the conditioned stimulus (CS) and an air puff as the unconditioned stimulus (US). The rabbits learned to discriminate between a CS paired with a US and delivered to one pontine nucleus (the CS+) and a CS presented alone and delivered to the contralateral pontine nucleus (the CS-). Subsequent reversal of the discrimination was also achieved when the CS+ and CS- stimulation sites were interchanged. The results are interpreted as support for the idea that essential plasticity for classical eyelid conditioning occurs efferent to the pontine nuclei, possibly in regions of the cerebellum.

Initial localization of the acoustic conditioned stimulus projection system to the cerebellum essential for classical eyelid conditioning.

Previous experiments have demonstrated a sufficient and necessary involvement of mossy fibers in projecting conditioned stimulus information to the cerebellum during classical eyelid conditioning in rabbits. Presented here are electrophysiological, anatomical, and lesion data that suggest that cells within the lateral pontine nuclear region may be essentially involved in projecting information concerning the occurrence of acoustic conditioned stimuli to the cerebellum during classical conditioning.

Is there—Or is there not—An influence of impulsiveness on classical eyelid conditioning?

Results of an experiment examining the relationship between the Eysenck's impulsiveness scale (I 5) and classical eyelid conditioning are reported. To this purpose the item content of past and present impulsiveness scales is examined and related to the eyelid conditioning performance of subjects high and low on the various impulsiveness scales. It was found that as long as impulsiveness is used in the narrow sense it is indeed a subscale in the Eysenck's personality description that is related to eyelid conditioning performance. Several issues concerning the role and place of impulsiveness in the three-dimensional space of psychoticism, extraversion and neuroticism are raised.

Rapid transfer of training occurs when direct mossy fiber stimulation is used as a conditioned stimulus for classical eyelid conditioning

Fifteen rabbits were classically conditioned using stimulation of the right pontine nuclei as a conditioned stimulus and a corneal airpuff as an unconditioned stimulus. After conditioning criterion was reached, the stimulation conditioned stimulus was transferred to the left pontine nuclei and the rate of conditioned response acquisition observed. Our results indicate that when electrodes were placed symmetrically in the right and left pontine nuclei, extremely rapid transfer of training occurred. Together with previous data, the present data supply further indirect evidence that the site of neural plasticity which underlies acquisition and retention of classically conditioned skeletal muscle responses is located efferent to the pontine nuclei, namely in the cerebellum.

A comparison of classical eyelid conditioning in adults and infants

In a classical conditioning procedure an eyeblink-eliciting tap to the glabella (the flat region of skin between the eyebrows) was presented 500 ms after the onset of a mild l-kHz tone. As tone-tap presentations proceeded, the probability of an eyeblink during the latter part of the tone increased in both infants (median age 8 months) and adults, but the infants were slower to condition than the adults and were more variable. Overall, the latency of the conditioned response to tone was significantly longer for infants than for adults, but the latency of the unconditioned response to tap was significantly shorter for infants than for adults.

Classical conditioning and retention of the infant's eyelid response: Effects of age and interstimulus interval

Independent groups of 10-, 20-, and 30-day-old infants were subjected to a classical eyelid conditioning procedure involving either a 500- or a 1500-msec interstimulus interval (ISI). Ten days later, all received a second conditioning session. A reliable increase in conditioned responding was observed at all ages but only by infants receiving the 1500-msec ISI. Although age was not a significant factor in any conditioning measure except final performance level, which was greater for the oldest than for the youngest group, it did influence long-term retention. A reliable memory component was observed in the Session 2 performance of infants initially trained at 20 and 30 days but not at 10 days. These data demonstrate the importance of temporal parameters in the formation of conditioned associations very early in infancy and provide evidence for the long-term behavioral consequences of those associations.

The influence of psychoticism and extraversion on classical eyelid conditioning using a paraorbital shock UCS

Abstract An experiment is described in which the effects of Psychoticism and Extraversion on classical eyelid conditioning were examined using a balanced design involving two levels of paraorbital shock intensity and two levels of response threshold. Questionnaire measures of Anxiety and Impulsivity were also analysed together with subjective ratings of the UCS. Results were broadly consistent with Eysenck's personality theory in that subjects scoring high on Psychoticism demonstrated lower levels of conditioning.