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)     

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)     

Ibotenic acid lesions of the medial septum retard delay eyeblink conditioning in rabbits (Oryctolagus cuniculus).

S. Berry and R. Thompson (1979) reported that electrolytic lesions of the medial septum significantly retard eyeblink conditioning. However, these electrolytic lesions were nonselective and may have also damaged the subcortical inputs to the hippocampus via the fimbria-fornix. In the present study, the medial septum was selectively lesioned with ibotenic acid in rabbits (Oryctolagus cuniculus), whose performance in a delay eyeblink conditioning paradigm was compared with that of intact controls, sham-operated controls, and intact controls given a systemic injection of scopolamine. Rabbits with selective medial septal lesions and rabbits receiving systemic scopolamine were significantly slower to condition than were intact and sham-lesioned rabbits. This finding demonstrates that the selective removal of the medial septum retards delay eyeblink conditioning in a manner similar to the disruption seen after systemic administration of scopolamine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prefrontal control of trace eyeblink conditioning in rabbits: Role in retrieval of the CR?

Rabbits (Oryctolagus cuniculus) were trained on a trace eyeblink (EB) conditioning task to a criterion of 10 consecutive EB conditioned responses (CRs). One week later, ibotenic acid or sham lesions were made in the mPFC centered on the prelimbic region (Brodmann's area 32) or the cingulate cortex (Brodmann's area 24). Following a 1-week postoperative recovery period, all animals were retrained for 4 consecutive days using the same parameters as during acquisition, given 1 week off, and retrained for another 4 days. Mean EB conditioning deficits in the group with area 32 lesions occurred on the first and second days of each retraining period. However, by the third and fourth days of retraining, these lesioned animals were performing at a level comparable to that of the sham group. Lesions of area 24 did not produce deficits at either retesting period. These findings were interpreted to indicate that area 32, but not area 24, is involved in retrieval processes, rather than consolidation or storage, in that the animals were impaired at both retesting times, but were able to relearn the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bilateral nature of the conditioned eyeblink response in the rabbit: Behavioral characteristics and potential mechanisms.

In Pavlovian eyeblink conditioning, the conditioned response (CR) is highly lateralized to the eye to which the unconditioned stimulus (US) has been directed. However, the initial conditioning of one eye can facilitate subsequent conditioning of the other eye, a phenomenon known as the intereye transfer (IET) effect. Because a conditioned emotional response (CER), as well as the eyeblink CR, is acquired during eyeblink conditioning and influences the development of the CR, the CER acquired in initial training can plausibly account for the IET effect. To evaluate this possibility, the present study utilized previously determined eyeblink conditioning procedures that effectively decouple the degree of CER and CR development to investigate the IET effect. In each of 3 experiments rabbits were initially trained with comparison procedures that differentially favored the development of the eyeblink CR or the CER, prior to a shift of the US to the alternate eye. The observed differences in the IET suggest that the effect depends largely on the specific development of eyeblink CRs rather than the CER. The neurobiological implications of this apparent bilaterality of the eyeblink CR are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of the cerebellar interpositus nucleus in short and long term memory for trace eyeblink conditioning.

In previous studies the cerebellar interpositus (IP) nucleus, but not the hippocampus, was shown to be necessary both for initial learning and retention and for long-term retention of the standard delay eyeblink conditioned response (CR). However, in the trace eyeblink CR procedure, the hippocampus is also necessary for initial learning and retention, but not for long-term retention. Here the authors evaluate the role of the IP nucleus in both initial learning and retention, and in long-term retention of the trace eyeblink CR, using muscimol infusion to reversibly inactivate the IP nucleus. For the short-term study, there were two subgroups, the first sequentially passed through acquisition, inactivation, and reacquisition phases, whereas the second subgroup went through inactivation, acquisition, and inactivation phases. For the long-term study, the rabbits acquired the CR and then rested for a month. Next, they were distributed into two subgroups: with or without retention training, and finally went through inactivation and reacquisition phases. The results showed that the prelearning IP nucleus inactivation prevented the acquisition of the trace CR, whereas the postlearning inactivation reversibly abolished the expression of both the short- and long-term CR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prefrontal control of trace versus delay eyeblink conditioning: Role of the unconditioned stimulus in rabbits (Oryctolagus cuniculus).

The conditioned eyeblink (EB) response was studied with trace conditioning procedures in rabbits (Oryctolagus cuniculus) with lesions to the medial prefrontal cortex (mPFC) or sham lesions. Three experiments were performed in which either periorbital shock or a corneal airpuff served as the unconditioned stimulus (US) in separate groups of sham or mPFC-lesioned rabbits. Acquisition of the EB conditioned response (CR) was faster and reached a higher asymptote with the eyeshock US than with the airpuff US. However, mPFC lesion-induced trace conditioning deficits were obtained only in the groups that received the airpuff US. All rabbits showed normal delay conditioning and extinction. These results suggest that mPFC mediates trace EB conditioning when emotional arousal is low. However, in circumstances when emotional arousal may be high (i.e., during exposure to aversive periorbital shock), other structures (such as amygdala) may be activated to permit learning even in the absence of input from mPFC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term retention of the classically conditioned eyeblink response in rats.

Retention of the classically conditioned eyeblink response in rats was tested with a conditioned stimulus (CS)-alone extinction test and 2 sessions of reacquisition training. Retention of the eyeblink conditioned response (CR) during both tests was highest 24 hrs and 1 mo after initial acquisition. Three months after initial acquisition, responding during the CS-alone test was at baseline, but there was significant savings during reacquisition. By 6 mo after initial acquisition, the memory for the eyeblink CR was not expressed in either test. The group differences in retention, despite initial acquisition of the eyeblink CR to equal levels, suggest that rat eyeblink conditioning may provide a useful behavioral model for studying the neural processes underlying memory retention and loss. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired delay eyeblink classical conditioning in individuals with anterograde amnesia resulting from anterior communicating artery aneurysm rupture.

Anterior communicating artery (ACoA) aneurysm rupture can lead to an anterograde amnesia syndrome similar to that observed after damage to the hippocampus and medial temporal lobes (MT). It is currently believed that ACoA amnesia results from basal forebrain damage that disrupts hippocampal processing without direct hippocampal damage. Converging evidence from animal studies and computational modeling suggests that qualitative differences may exist in the pattern of memory impairment after basal forebrain or MT damage. For example, animals with basal forebrain but not hippocampal damage are impaired at delay eyeblink classical conditioning (EBCC). In this study, individuals with ACoA amnesia were shown to be impaired at delay EBCC compared with matched controls; this contrasts with the spared delay EBCC previously observed in MT amnesia. This finding suggests the beginning of a possible dissociation between the memory impairments in MT versus ACoA amnesia. (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)     

Medial prefrontal cortex and Pavlovian conditioning: Trace versus delay conditioning.

Pavlovian eyeblink (EB) conditioning was studied in both trace and delay paradigms in rabbits (Oryctolagus cuniculus) with either medial prefrontal cortex (mPFC) lesions or sham lesions. mPFC lesions of prelimbic cortex (Brodmann's Area 32) retarded EB conditioning in the trace but not the delay paradigm. However, this effect was significant only when the conditioned stimulus (CS) was 500 rather than 100 ms in duration. Lesions of the anterior cingulate cortex (Area 24) did not affect EB conditioning in a trace paradigm. Accompanying CS-evoked heart rate slowing was attenuated under all conditions by the mPFC lesions, although this result was not always statistically significant. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal theta-band activity and trace eyeblink conditioning in rabbits.

The authors examined the relationship between hippocampal theta activity and trace eyeblink conditioning. Hippocampal electrophysiological local field potentials were recorded before, during, and after conditioning or explicitly unpaired training sessions in adult male New Zealand White rabbits. As expected, a high relative power of theta activity (theta ratio) in the hippocampus predicted faster acquisition of the conditioned response during trace conditioning but, contrary to previous results obtained using the delay paradigm, only in the initial stage of learning. The presentation of the conditioned stimulus overall elicited an increase in the hippocampal theta ratio. The theta ratio decreased in the unpaired group as a function of training, remained high throughout conditioning in the fast learners, and rapidly increased in the slow learners initially showing a low theta ratio. Our results indicate a reciprocal connection between the hippocampal oscillatory activity and associative learning. The hippocampal theta ratio seems to reflect changes and differences in the subjects’ alertness and responsiveness to external stimuli, which affect the rate of learning and are, in turn, affected by both conditioning and unpaired training. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Eyeblink conditioning during an interstimulus interval switch in rabbits (Oryctolagus cuniculus) using picrotoxin to disrupt cerebellar cortical input to the interpositus nucleus.

The role of the cerebellar cortex in eyeblink classical conditioning remains unclear. Experimental manipulations that disrupt the normal function impair learning to various degrees, and task parameters may be important factors in determining the severity of impairment. This study examined the role of cerebellar cortex in eyeblink conditioning under conditioned stimulus?unconditioned stimulus intervals known to be optimal or nonoptimal for learning. Using infusions of picrotoxin to the interpositus nucleus of the rabbit cerebellum, the authors pharmacologically disrupted input from the cerebellar cortex while training with an interstimulus interval (ISI)-switch procedure. One group of rabbits (Oryctolagus cuniculus) was 1st trained with a 250-ms ISI (optimal) and then switched to a 750-ms ISI (nonoptimal). A 2nd group was trained in the opposite order. The most striking effect was that picrotoxin-treated rabbits initially trained with a 250-ms ISI learned comparably to controls, but those initially trained with a 750-ms ISI were severely impaired. These results suggest that functional input from cerebellar cortex becomes increasingly important for the interpositus nucleus to learn delay eyeblink conditioning as the ISI departs from an optimal interval. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exploring prefrontal cortical memory mechanisms with eyeblink conditioning.

Several studies in nonhuman primates have shown that neurons in the dorsolateral prefrontal cortex have activity that persists throughout the delay period in delayed matching to sample tasks, and age-related changes in the microcolumnar organization of the prefrontal cortex are significantly correlated with age-related declines in cognition. Activity that persists beyond the presentation of a stimulus could mediate working memory processes, and disruption of those processes could account for memory deficits that often accompany the aging process. These potential memory and aging mechanisms are being systematically examined with eyeblink conditioning paradigms in nonprimate mammalian animal models including the rabbit. The trace version of the conditioning paradigm is a particularly good system to explore declarative memory since humans do not acquire trace conditioning if they are unable to become cognitively aware of the association between a conditioning tone and an airpuff to the eye. This conditioning paradigm has been used to show that the hippocampus and cerebellum interact functionally since both conditioned responses and conditioned hippocampal pyramidal neuron activity are abolished following lesions of the cerebellar nuclei and since hippocampal lesions prevent or abolish trace conditioned blinks. However, because there are no direct connections between the hippocampal formation and the cerebellum, and because the hippocampus is not necessary for trace conditioning after a period of consolidation has elapsed, we and others have been examining the prefrontal cortex for its role in forebrain-dependent trace eyeblink conditioning. This review examines some of the literature which suggests that the prefrontal cortex serves to orchestrate a neuronal network that interacts with the cerebellum to mediate adaptively timed conditioned responses. (PsycINFO Database Record (c) 2011 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)     

Eyeblink conditioning leads to fewer synapses in the rabbit cerebellar cortex.

Eyeblink conditioning involves the pairing of a conditioned stimulus (tone) to an aversive unconditioned stimulus (air puff). Although the circuitry that underlies this form of learning is well defined, synaptic changes in these structures have not been fully investigated. This experiment examined synaptic structural plasticity in the cerebellar cortex, a structure that has been found to modulate the acquisition and timing of the conditioned response. Long-term depression of Purkinje cells (PCs) in the cerebellar cortex has been proposed as a mechanism for releasing inhibition of the interpositus nuclei, a structure critical for the formation of the CR. Adult albino rabbits were randomly allocated to either a paired, unpaired, or exposure-only condition. The results showed a significant decrease in the number of excitatory synapses in the outer layer of the cerebellar cortex in the conditioned rabbits compared with controls. This finding suggests that a reduction in the number of excitatory synapses may contribute to the lasting depression of PC activity that is associated with eyeblink conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spared discrimination and impaired reversal eyeblink conditioning in patients with temporal lobe amnesia.

The effect of medial temporal lobe damage on a 2-tone delay discrimination and reversal paradigm was examined in human classical eyeblink conditioning. Eight medial temporal lobe amnesic patients and their demographically matched controls were compared. Amnesic patients were able to distinguish between 2 tones during the initial discrimination phase of the experiment almost as well as control participants. Amnesic patients were not able to reverse the previously acquired 2-tone discrimination. In contrast, the control participants showed improved discrimination performance after the reversal of the tones. These findings support the hypothesis that the hippocampus and associated temporal lobe regions play a role in eyeblink conditioning that becomes essential in more complex versions of the task, such as the reversal of an acquired 2-tone discrimination. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Posttraining lesions of the medial prefrontal cortex impair performance of Pavlovian eyeblink conditioning but have no effect on concomitant heart rate changes in rabbits (Oryctolagus cuniculus).

The medial prefrontal cortex (mPFC) plays a critical role in conditioned autonomic adjustments but is not involved in classically conditioned somatomotor responses unless the training conditions include reversal or trace conditioning. The studies showing these effects have all used pretraining lesions. The present study assessed the effects of posttraining lesions on eyeblink (EB) and heart rate (HR) conditioned responses (CRs) in both delay and trace conditioning paradigms in the rabbit (Oryctolagus cuniculus). Posttraining lesions lowered the percentage of EB CRs during retesting compared with pretesting levels for both delay and trace conditioning. Control lesions and pretraining lesions produced no significant effects during retesting. Posttraining lesions had no effect on the HR CR. These findings suggest that a critical mechanism in the mPFC is involved in retrieval of information during EB conditioning but that the mPFC integration of autonomic and somatomotor processes is not critical to this retrieval process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)