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)     

Procedural memory system supports single cue trace eyeblink conditioning in medial temporal lobe amnesia.

A number of studies investigating trace eyeblink conditioning have found impaired, but not eliminated, acquisition of conditioned responses (CRs) in both animals and humans with hippocampal removal or damage. The underlying mechanism of this residual learning is unclear. The present study investigated whether the impaired level of learning is the product of residual hippocampal function or whether it is mediated by another memory system that has been shown to function normally in delay eyeblink conditioning. Performance of bilateral medial temporal lobe amnesic patients who had a prior history of participating in eyeblink conditioning studies was compared to a control group with a similar training history and to an untrained control group in a series of single cue trace conditioning tasks with 500 ms, 250 ms, and 0 ms trace intervals. Overall, patients acquired CRs to a level similar to the untrained controls, but were significantly impaired compared to the trained controls. The pattern of acquisition suggests that amnesic patients may be relying on the expression of previously acquired, likely cerebellar based, procedural memory representations in trace conditioning. (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)     

Conditional Discrimination Learning in Patients With Bilateral Medial Temporal Lobe Amnesia.

The ability of bilateral medial temporal lobe amnesic patients (MT; n=8) and normal participants (NC; n=8) to acquire a conditional discrimination in trace and delay eyeblink conditioning paradigms was investigated. Experiment 1 assessed trace conditional discrimination learning by using a light conditional stimulus (S+/S-) and tone conditioned stimulus (CS) separated by a 1-s trace. NCs responded differentially on S+ trials (mean percent conditioned responses=66) versus S- trials (30). Whereas MTs were impaired in their acquisition of the conditional discrimination (S+=51, S-=43). In Experiment 2, the temporal separation was eliminated. NCs acquired the conditional discrimination (S+=70, S-=29). MTs were unable to respond differentially (S+=42, S-=37). The findings indicate that the hippocampal system is essential in acquiring a conditional discrimination, even in a delay paradigm. (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)     

Decremental effects of context exposure following delay eyeblink conditioning in rabbits.

The conditioning context arises from the relatively static features of the training environment. In rabbit eyeblink conditioning, procedures that retard acquisition (conditioned stimulus [CS] preexposure, unconditioned stimulus preexposure, blocking manipulations) are attenuated by context changes. In this article the authors investigate the effect of context exposure after initial delay conditioning. After conditioned responses (CRs) were established, one group received 6 sessions of context exposure, whereas control groups either remained in their home cages or received exposure to handling and a novel context. Thereafter, all groups received CS-alone testing. The expression of CRs was substantially reduced following context exposure relative to any retention loss in the home-cage control. Exposure to handling and a novel context facilitated the CRs rather than reducing them. (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)     

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)     

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)     

Content-specific source encoding in the human medial temporal lobe.

Although the medial temporal lobe (MTL) is known to be essential for episodic encoding, the contributions of individual MTL subregions remain unclear. Data from recognition memory studies have provided evidence that the hippocampus supports relational encoding important for later episodic recollection, whereas the perirhinal cortex has been linked with encoding that supports later item familiarity. However, extant data also strongly implicate the perirhinal cortex in object processing and encoding, suggesting that perirhinal processes may contribute to later episodic recollection of object source details. To investigate this possibility, encoding activation in MTL subregions was analyzed on the basis of subsequent memory outcome while participants processed novel scenes paired with 1 of 6 repeating objects. Specifically, encoding activation correlating with later successful scene recognition memory was evaluated against that of source recollection for the object paired with the scene during encoding. In contrast to studies reporting a link between perirhinal cortex and item familiarity, it was found that encoding activation in the right perirhinal cortex correlates with successful recollection of the paired object. Furthermore, other MTL subregions also exhibited content-specific source encoding patterns of activation, suggesting that MTL subsequent memory effects are sensitive to stimulus category. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Confirmatory factor analysis of the WMS-III in patients with temporal lobe epilepsy.

Five competing models specifying the factor structure underlying the Wechsler Memory Scale--Third Edition (D. Wechsler, 1997b) primary subtest scores were evaluated in a sample of patients with intractable temporal lobe epilepsy (N=254). Models specifying separate immediate and delayed constructs resulted in inadmissible parameter estimates and model specification error. There were negligible goodness-of-fit differences between a 3-factor model of working memory, auditory memory, and visual memory and a nested--more parsimonious--2-factor model of working memory and general memory. The results suggest that specifying a separate visual memory factor provides little advantage for this sample--an unexpected finding in a population with lateralized dysfunction, for which one might have predicted separate auditory and visual memory dimensions. (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)     

Preserved monitoring and control processes in temporal lobe epilepsy.

Objective: The aim of this study was to assess an aspect of metamemory never examined before in patients with temporal lobe epilepsy (TLE): the ability to upgrade the accuracy of one's memory predictions after study. Method: Four lists of different levels of difficulty and relatedness were presented to 15 TLE patients and 15 control participants, who were asked to predict their subsequent recall both before and after studying each list. Results: The results showed clear impairment in recall in TLE patients. However, both TLE patients and controls showed an improvement in accuracy in their poststudy predictions compared with their prestudy predictions, showing that both groups were able to upgrade their metamemory predictions. Unexpectedly, prediction accuracy was overall higher in TLE patients than in controls. Moreover, study time was allocated in both groups taking into account the characteristics of the list. Conclusion: These results confirm and extend findings of Howard et al. (2010) of intact metamemory in TLE patients, and provide further support to the dissociation between memory and metamemory in this clinical population. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Memory for famous people in patients with unilateral temporal lobe epilepsy and excisions.

Memory for famous individuals was assessed by the use of a recognition test in which participants first made familiarity judgments, followed by forced-choice decisions to specific probes for identity. Patients with temporal lobe epilepsy (TLE) or excisions, 12 left hemisphere and 12 right hemisphere, and 18 control participants identified famous figures across 3 decades (1970s-1990s). Only patients with right TLE were impaired at familiarity judgments of faces; this deficit was evident only for the most recent decades. Both groups of patients, however, were impaired at naming famous faces and at providing semantic information about famous people. These findings suggest the integrity of temporal structures in both hemispheres is critical for retrieval of detailed semantic information about famous individuals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inactivation of sodium channel Scn8A (Nav1.6) in purkinje neurons impairs learning in Morris Water Maze and delay but not trace eyeblink classical conditioning.

To examine the isolated effects of altered currents in cerebellar Purkinje neurons, the authors used Scn8aflox/flox, Purkinje cell protein-CRE (Pcp-CRE) mice in which Exon 1 of Scn8a is deleted only in Purkinje neurons. Twenty male Purkinje Scn8a knockout (PKJ Scn8a KO) mice and 20 male littermates were tested on the Morris water maze (MWM). Subsequently, half were tested in 500-ms delay and half were tested in 500-ms trace eyeblink conditioning. PKJ Scn8a KO mice were impaired in delay conditioning and MWM but not in trace conditioning. These results provide additional support for the necessary participation of cerebellar cortex in normal acquisition of delay eyeblink conditioning and MWM and raise questions about the role, if any, of cerebellar cortex in trace eyeblink conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

NMDA and D2-like receptors modulate cognitive flexibility in a color discrimination reversal task in pigeons.

Reversal and extinction learning represent forms of cognitive flexibility that refer to the ability of an animal to alter behavior in response to unanticipated changes on environmental demands. A role for dopamine and glutamate in modulating this behavior has been implicated. Here, we determined the effects of intracerebroventricular injections in pigeons' forebrain of the D2-like receptor agonist quinpirole, the D2-like receptor antagonist sulpiride and the N-methyl-d-aspartate receptor antagonist AP-5 on initial acquisition and reversal of a color discrimination task. On day one, pigeons had to learn to discriminate two color keys. On day two, pigeons first performed a retention test, which was followed by a reversal of the reward contingencies of the two color keys. None of the drugs altered performance in the initial acquisition of color discrimination or affected the retention of the learned color key. In contrast, all drugs impaired reversal learning by increasing trials and incorrect responses in the reversal session. Our data support the hypothesis that D2-like receptor mechanisms, like N-methyl-d-aspartate receptor modulations, are involved in cognitive flexibility and relearning processes, but not in initial learning of stimulus-reward association. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lateralization of the startle reflex circuit in humans: An examination with monaural probes following unilateral temporal lobe resection.

Startle reflex (SR) modulation elicited by monaural probes during affective picture viewing was investigated in patients following left temporal lobectomy (LTL; n = 8) and right temporal lobectomy (RTL; n = 10) and in controls (n = 18). All patients had undergone anteromedial temporal lobe (ATL) resection. LTL participants exhibited attenuated overall SR magnitude. Affective SR modulation in controls was significant for left ear probes, at both eyes, but not for right ear probes. RTL but not LTL participants displayed significant startle attenuation during pleasant picture viewing. Results suggest that monaural startle probes primarily activate structures in the ipsilateral ATL and that the ATLs are interconnected, with the left ATL more critical in perceiving arousing properties of affective stimuli, necessary for affective SR modulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Single neurons in the medial prefrontal cortex of the rat exhibit tonic and phasic coding during trace fear conditioning.

Trace fear conditioning is a learning task that requires the association of an auditory conditioned stimulus (CS) and a shock unconditioned stimulus (US) that are separated by a 20-s trace interval. Single neuron activity was recorded from the prelimbic and infralimbic areas of the medial prefrontal cortex in rats during trace fear conditioning or nonassociative unpaired training. Prelimbic neurons showed learning-related increases in activity to the CS and US, whereas infralimbic neurons showed learning-related decreases in activity to these stimuli. A subset of prelimbic neurons exhibited sustained increases in activity during the trace interval. These sustained prelimbic responses may provide a bridging code that allows for overlapping representations of CS and US information within the trace fear conditioning circuit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual and cued fear conditioning in C57BL/6J and DBA/2J mice: Context discrimination and the effects of retention interval.

Context discrimination and time course studies of contextual fear conditioning revealed strain differences between C57BL/6J (B6) and DBA/2J (D2) mice. Both strains discriminated contexts, but D2 mice exhibited less freezing in a shock-paired context. The strains did not differ immediately, or at 2 and 3 hr after contextual fear conditioning training. D2 mice showed less freezing at 15 min, 30 min, and 24 hr after training. B6 mice exhibited exaggerated generalized freezing and poor discrimination between the context and altered context 7-30 days after training. The acoustic startle response in B6 mice was also enhanced at 14 days after training. D2 mice did not show this pattern of generalized freezing. B6, but not D2, mice retained contextual memories for at least 60 days. (PsycINFO Database Record (c) 2010 APA, all rights reserved)