Awareness in classical differential eyeblink conditioning in young and aging humans.

The role of awareness and its impact on learning the conditioned eyeblink response was investigated in both trace and delay discrimination eyeblink conditioning in young and aging participants, in 4 paradigms: delay 750, delay 1250, trace 500, and trace 1000. Participants concurrently watched a silent movie about which they were questioned afterward. Acquisition in both the trace and delay discrimination task was correlated with awareness of conditioning stimulus contingencies, regardless of age. Age-dependent deficits were observed in trace discrimination but not in delay discrimination, with more severe deficits appearing at the longer trace interval. The percentage of aware participants was also found to be greater in the young population than in the aging population. These results indicate that awareness or knowledge of stimulus contingencies may be an important contributor to successful acquisition in higher order discrimination tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Number of trials to assess human eyeblink classical conditioning.

Eyeblink classical conditioning ( EBCC) is a useful paradigm for studying the neurobiology of learning and memory. EBCC shows large age effects and has been shown to be sensitive to Alzheimer-like neuropathology. The EBCC data of 241 participants, including young, middle-aged, and elderly normal adults, adults with Down's syndrome, and patients with probable Alzheimer's disease, were analyzed to identify a minimum number of trials for reliable assessment. Results indicate that EBCC performance can be as reliably assessed in 63 trials as in 90 trials. Using fewer conditioning trials reduces administration time, making EBCC more practical for both research and potential diagnostic purposes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cerebellar involvement in eyeblink classical conditioning in humans.

The role of the ipsilateral cerebellum in human eyeblink conditioning was investigated using the 400-ms delay paradigm and testing 14 cerebellar patients (7 with unilateral lesions and 7 with bilateral lesions) and 20 control participants. Patients performed significantly worse with the ipsilesional eye than control participants but showed no difference when tested with the contralesional eye. Conditioned responses (CRs) totaled 14% for all patients in comparison with 60% for control participants. Data on timed-interval tapping for 6 patients and 14 control participants showed that clock variability was greater with the ipsilesional hand in patients. Only clock variability correlated significantly with percentage of CRs in control participants. Comparisons of paired associate learning and memory for 8 patients and 14 control participants revealed no significant differences. Results confirm that the ipsilateral cerebellum plays a role in eyeblink classical conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Training to criterion in eyeblink classical conditioning in Alzheimer's disease, Down's syndrome with Alzheimer's disease, and healthy elderly.

The cholinergic antagonist scopolamine delays acquisition of eyeblink classical conditioning (EBCC) in rabbits and humans, but scopolamine-treated organisms eventually acquire conditioned responses (CRs). Patients with probable Alzheimer's disease (AD) and older adults with Down's syndrome (DS/AD) have disrupted cholinergic systems and perform EBCC very poorly. It was hypothesized that patients with probable AD and DS/AD, like scopolamine-injected organisms, would acquire CRs if given sufficient training. Twelve probable AD patients, 12 DS/AD patients, and 6 healthy elderly control individuals participated in 5 daily 90-trial sessions of EBCC. Fifty-eight percent of the probable AD, 92% of the DS-AD, and 100% of the control participants achieved learning criterion. Probable AD, DS/AD, and control participants had statistically significant increases in the percentage of CRs produced over 5 EBCC sessions. The neural substrate for EBCC was not eliminated in probable AD or DS/AD patients, although the learning mechanism was disrupted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nicotinic cholinergic system involvement in eyeblink classical conditioning in rabbits.

A nicotinic cholinergic antagonist, mecamylamine (MEC), was administered to rabbits tested on eyeblink classical conditioning (EBCC) in the 750-msec delay paradigm for 10 90-trial sessions. Nicotinic receptors were measured in 3 brain regions in S treatment groups: paired conditioned stimulus–unconditioned stimulus (CS–UCS) presentations with (1) vehicle, young; (2) vehicle, older; (3) 0.5 mg/kg MEC, young; unpaired CS–UCS with (4) 0.5 mg/kg MEC, young; and (5) vehicle, young. Daily MEC injections disrupted acquisition in young rabbits (769 trials to learning criterion vs 323 trials for vehicle-treated young rabbits). MEC-treated young rabbits learned similarly to older rabbits. Brain nicotinic receptors were not affected by 10 daily MEC injections. To our knowledge, this experimental protocol, using a low MEC dose to selectively inhibit nicotinic cholinergic receptors, is the first to demonstrate a role for nicotinic cholinergic receptors in EBCC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delay eyeblink classical conditioning is impaired in Fragile X syndrome.

The authors examined 400 ms delay eyeblink classical conditioning in 20 participants with Fragile X syndrome ages 17 to 77 years, and 20 age-matched, healthy control participants. The participants in the Fragile X group demonstrated impaired learning and abnormal conditioned response timing. Adults with Fragile X (n = 16) were also tested at two successive 12-month follow-up sessions to examine reacquisition and long-term retention. Participants in groups who were older and younger than 45 years demonstrated significant learning during each reacquisition session. Younger participants demonstrated greater retention of the conditioned stimulus/unconditioned stimulus association at each follow-up session than older participants. Fragile X impairs the acquisition and timing of conditioned eyeblink responses, but with repeated training adults with Fragile X syndrome show significant plasticity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Standard delay eyeblink classical conditioning is independent of awareness.

P. F. Lovibond and D. R. Shanks (see record 2002-00340-001) suggested that all forms of classical conditioning depend on awareness of the stimulus contingencies. This article considers the available data for eyeblink classical conditioning, including data from 2 studies (R. E. Clark, J. R. Manns, & L. R. Squire, 2001; J. R. Manns, R. E. Clark, & L. R. Squire, 2001) that were completed too recently to have been considered in their review. In addition, in response to questions raised by P. F. Lovibond and D. R. Shanks, 2 new analyses of data are presented from studies published previously. The available data from humans and experimental animals provide strong evidence that delay eyeblink classical conditioning (but not trace eyeblink classical conditioning) can be acquired and retained independently of the forebrain and independently of awareness. This conclusion applies to standard conditioning paradigms; for example, to single-cue delay conditioning when a tone is used as the conditioned stimulus (CS) and to differential delay conditioning when the positive and negative conditioned stimuli (CS+ and CS-) are a tone and white noise. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delay discrimination and reversal eyeblink classical conditioning in abstinent chronic alcoholics.

[Correction Notice: An erratum for this article was reported in Vol 23(2) of Neuropsychology (see record 2009-02621-003). The lifetime drinking data listed in Table 1 on p. 198 was not correctly calculated and underestimated lifetime exposure to alcohol. The corrected lifetime variables from that table are included.] Evidence has shown that alcoholism leads to volume reductions in brain regions critical for associative learning using the eyeblink classical conditioning paradigm (EBCC). Evidence indicates that cerebellar shrinkage causes impairment in simple forms of EBCC, whereas changes in forebrain structures result in impairment in more complex tasks. In this study, the ability of abstinent alcoholics and matched control participants to acquire learned responses during delay discrimination and discrimination reversal was examined and related to severity of drinking history and neuropsychological performance. During discrimination learning, one tone (CS+) predicted the occurrence of an airpuff (unconditioned stimulus), and another tone (CS-) served as a neutral stimulus; then the significance of the tones was reversed. Alcoholics who learned the initial discrimination were impaired in acquiring the new CS+ after the tones reversed; this is a function that has previously been linked to forebrain structures. It is suggested that a factor important to alcoholic addiction may be the presence of alcoholic-related associative responses that interfere with the ability to learn new more adaptive associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mediodorsal thalamic lesions and Pavlovian conditioning of heart rate and eyeblink responses in the rabbit.

Rabbits received ibotenic acid lesions of the mediodorsal nucleus of the thalamus (MD) or sham lesions. These animals were compared on 4 sessions of Pavlovian eyeblink and heart rate conditioning, in which a tone was the conditioned stimulus/stimuli (CS) and a paraorbital electrical shock was the unconditioned stimulus/stimuli (UCS). Lesions of MD retarded acquisition of the eyeblink conditioned response (CR) and abolished the late-occurring tachycardiac component of the heart rate CR. The data are compatible with previous experiments (H. Groenewegen, 1988), suggesting that MD participated in the sympathetic control associated with somatomotor learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Predictors of eyeblink classical conditioning over the adult age span.

The major aim was to identify predictors of the large age differences that exist in eyeblink classical conditioning. Eyeblink conditioning was assessed in 190 participants over the age range of 20–89 years, with 150 trained in the paired condition and 40 trained in the explicitly unpaired control condition. Timed-interval tapping was used to assess cerebellar function. Blink reaction time and explicit learning and memory were also assessed. Stepwise multiple regression indicated that the effect of age accounted for the largest proportion of the variance, but the cerebellar measure also predicted eyeblink conditioning at a significant level. Reaction time and explicit memory measures did not account for a significant amount of the variance in eyeblink conditioning. Age-related effects in the cerebellum apparently affect timing and learning in normal adults. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal activity during classical discrimination—Reversal eyeblink conditioning in rabbits.

Multiple-unit neuronal recordings were taken from the hippocampi of 10 male, New Zealand white rabbits during classical discrimination and reversal eyeblink conditioning using 2 tones as the conditioned stimuli (CS+ and CS–) and an air-puff unconditioned stimulus. During discrimination training, characteristic learning-related activity was seen in the hippocampus on trials when a conditioned response (CR) was executed. During early phases of reversal training, however, when high numbers of CRs were evident to both the new CS+ (the former CS–) and the new CS– (the former CS+), no learning-related activity was observed. Characteristic CR-related hippocampal activity to the CS+ was observed only after the rabbits began to learn the reversal response. These results suggest that the hippocampus may encode different features of eyeblink conditioning during discrimination and reversal learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of respiration on heart rate in an aversive classical conditioning situation.

Previous research has attempted to assess respiratory influences on the cardiac response in anticipation of shock. These studies have utilized either control of rate of respiration, sustained inhalation or exhalation, control of amplitude of respiration, or some combination of these. In the present study, 30 18-25 yr. Old male undergraduate ss inhaled at the start of each trial, held their breath, exhaled during a 4-sec tone, and then refrained from breathing in again until they received an electric shock. Thus, each trial corresponded to 1 breath cycle. Cs-ucs interval and duration of breath holding were varied orthogonally. The 3 major findings were: (a) a reliable, large magnitude (20 bpm) deceleration followed the inhalation at the start of each trial; (b) the acceleratory component of the cardiac response in anticipation of shock increased with cs-ucs pairings, and therefore could not be considered an orienting reflex; and (c) the biphasic form of the cardiac response occurred over an 8-10 sec. Period, regardless of cs-ucs interval, and appeared to be "locked" to the cs rather than to the ucs. (french summary) (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multiple somatic measures and heart rate during classical aversive conditioning in the cat.

In 2 experiments, a total of 9 freely moving cats were subjected to classical aversive conditioning under either a delay or a trace paradigm using a tone conditioned stimulus (CS) and a shock unconditioned stimulus (UCS). During a 7- or 9-sec CS-UCS interval, heart rate (HR) decelerated and concomitantly, general activity, neural activity in the pyramidal motor system, respiration amplitude, and neck muscle electromyogram (EMG) decreased. General activity and pyramidal activity were more related to HR than were respiration and EMG. The close correspondence between HR and the various measures of somatic activity are interpreted as showing the dependence of HR change on the metabolic demands of the organism. The concomitance demonstrated between HR change and somatic change provides further evidence against HR change as a direct index of emotional or motivational processes. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Imagery in human classical conditioning.

Many clinical strategies use patients' imagery to explore and treat phobic and posttrauma reactions, however little attention has been paid to the underlying assumption that imagery of relevant stimuli may help maintain conditioned behavior. In this article, the authors examine the premise that mental images can potentiate and substitute for physical stimuli in human classical conditioning. The authors review empirical evidence to detail the role of images of conditioned stimuli (CS) and unconditioned stimuli (US) during pre-exposure to stimuli, the actual pairing of the CS and US, and extinction when the CS is presented alone. The evidence suggests that mental imagery can facilitate or diminish the outcome of classical conditioning in humans and, more tentatively, that mental images can substitute for actual US and CS in autonomic conditioning. They argue that researchers should explore the role of mental imagery in conditioning through the use of advances in the measurement of imagery. Finally, they analyze anxiety and trauma reactions as examples of how applied areas can be used to explore and benefit from developments in this area. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of aging in delay and trace human eyeblink conditioning.

Normal aging has been shown to impact performance during human eyeblink classical conditioning, with older adults showing lower conditioning levels than younger adults. Previous findings showed younger adults can acquire both delay and trace conditioning concurrently, but it is not known whether older adults can learn under the same conditions. Present results indicated older adults did not produce a significantly greater number of conditioned responses during acquisition, but their ability to time eyeblink responses prior to the unconditioned stimulus was preserved. The decline in eyeblink conditioning that typically accompanies aging has been extended to concurrent presentations of delay and trace conditioning trials. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Extracellular amino acid levels in the interpositus nucleus during classical eyeblink conditioning in alert cats.

The extracellular levels of selected amino acids in the cerebellar posterior interpositus nucleus (PIN) during classical eyeblink conditioning was analyzed in alert cats using a delay paradigm. Animals were prepared for the chronic recording of eyelid movements (with the magnetic search-coil technique) and the electromyographic activity of the orbicularis oculi muscle. With the help of a guide and push-pull cannulae, selected PIN sites were perfused daily during classical eyeblink conditioning. The perfusate was sampled at intervals of 5 min and analyzed with a high-pressure liquid chromatography- electrochemical detection (HPLC-EC) method. The analysis of push-pull perfusate revealed a significant increase in the release of glycine, taurine, and glutamate across the successive conditioning sessions, in parallel with the acquisition of eyelid conditioned responses (CRs). Both CRs and extracellular levels of these three amino acids returned to control values during extinction. Other amino acids (alanine, GABA, glutamine, serine, and threonine) did not undergo modifications in their extracellular concentrations across the training. Results are discussed with regard to the role of PIN in this type of associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Autonomic control of heart rate and blood pressure in spontaneously hypertensive rats during aversive classical conditioning.

Examined heart rate (HR) and blood pressure (BP) responses of 26 spontaneously hypertensive rats (SHR) and 21 genetically-controlled Wistar/Kyoto (WKY) rats during aversive classical conditioning. Assessments were made of the effects of selective autonomic blockade by methyl atropine (10 mg/kg), phentolamine (2 mg/kg), and propranolol (2 mg/kg). The decelerative SHR HR CR was not secondary to baroreceptor reflex activity, although such activity was involved in the pressor BP and decelerative HR orienting response (OR) and UCR complex of the SHRs on initial applications of the CS and UCS. Augmented pressor BP ORs, CRs, and UCRs in the SHRs and differential drug effects on BP and HR baselines of the 2 strains suggested the presence of enhanced sympathetic activity in the SHRs that was not reflected in the SHR decelerative HR CR. Phentolamine unmasked evidence of reflex beta?-vasodilation deficiency in the SHRs that could have contributed to the enhancement of their BP OR and CR. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective autonomic blockades: Effects upon classical conditioning of heart rate and lever-lift suppression in rabbits.

Studied heart rate, blood pressure, and lever lifting during differential classical conditioning in 2 experiments with a total of 8 female Belgian hares. The unconditioned stimulus was electrical stimulation of the septal region or the hypothalamus through chronically implanted electrodes; the conditioned stimuli were 2 tones differing in frequency. Beta-adrenergic blockade by propranolol did not affect cardiovascular unconditioned responses (bradycardia and pressor UCRs), conditioned responses (bradycardia CRs), or lever-lift responses. Cholinergic blockade by atropine methylnitrate abolished heart-rate responses but not lever-lift responses. Findings suggest that heart-rate responses were mediated by increases in vagal tone. Alpha-adrenergic blockade by phentolamine abolished bradycardia and pressor UCRs, but not bradycardia CRs. It is also suggested that separate central mechanisms mediated bradycardia UCRs and CRs. Removal of the lever diminished without eliminating bradycardia CRs, indicating partial independence between lever-lift and cardiac CRs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A computational model of cholinergic disruption of septohippocampal activity in classical eyeblink conditioning

Aspartate-like immunoreactivity was visualized in the neostriatum of rats using indirect immunofluorescence techniques and antibodies raised against aspartate conjugated to keyhole limpet hemocyanine. In normal rats only a few aspartate-positive cell bodies with limited processes were observed. A moderate increase was seen after treatment with (+)methamphetamine and haloperidol. A dramatic increase in the number and fluorescence intensity was observed in the unilaterally 6-hydroxy-dopamine lesioned rats after multiple injections of the D1-dopamine receptor agonist SKF 38393. In these rats strongly fluorescent processes as well as extensive terminal varicose fibre networks were observed. This increase could partly be blocked by the D1-dopamine receptor antagonist SCH 23390. Using a modified technique the aspartate-positive cell bodies and processes were observed even when the antiserum was diluted 1:80,000. Positive cell bodies and fibres were also seen on the ipsilateral side outside the neostriatum, for example in the islet of Calleja and in the piriform cortex. The aspartate-positive cells were negative for dopamine- and cyclic AMP-regulated phosphoprotein-32, a marker for neurons bearing dopamine D1-receptor subtype. A proportion of the aspartate-positive neurons (20%) contained neuropeptide tyrosine-like immunoreactivity. On adjacent sections there was a marked up-regulation of preprodynorphin-like immunoreactivity. The up-regulation of dynorphin and aspartate was only observed when there was an almost complete denervation of the neostriatum as visualized with antiserum to tyrosine hydroxylase, a marker for dopamine fibres. The present results raise the possibility that aspartate may act as a neurotransmitter released from interneurons in the neostriatum.