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)     

Medial Prefrontal Lesions and Pavlovian Eyeblink and Heart Rate Conditioning: Effects of Partial Reinforcement on Delay and Trace Conditioning in Rabbits (Oryctolagus cuniculus).

Effects of continuous (100%) versus partial (25%) reinforcement were studied on Pavlovian delay and trace eyeblink conditioning in rabbits (Oryctolagus cuniculus) with either lesions to the medial prefrontal cortex (mPFC) or sham lesions. Concomitant heart rate changes evoked by the conditioned stimulus were also assessed. Partial reinforcement retarded eyeblink conditioning in both the trace and delay paradigm, but this impairment was greater during trace conditioning and in rabbits with mPFC lesions. Accompanying conditioned stimulus-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)     

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)     

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 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)     

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)     

Involvement of the rat medial prefrontal cortex in novelty detection.

The prefrontal cortex in humans has been implicated in processes that underlie novelty detection and attention. This study examined the contribution of the rat medial prefrontal cortex to novelty detection using the targeting, or orienting, response (OR) as a behavioral index. Lesions to the medial prefrontal cortex (specifically the prelimbic and infralimbic cortices) influenced neither the OR to a novel visual stimulus from a localized light source (V1), nor the change in this OR over the course of a series of exposures to V1. However, after exposure to V1, the OR to a 2nd visual stimulus from the same source, V2, was more pronounced in control rats than in lesioned rats. These results suggest that the medial prefrontal cortex in the rat contributes to the process of novelty detection. (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)     

Studies of binaural detection in the rabbit (Oryctolagus cuniculus) with Pavlovian conditioning.

A Pavlovian conditioned eyeblink response in rabbits (Oryctolagus cuniculus) was used to study psychoacoustical phenomena previously demonstrated in human listeners and other animals. This article contains the results of a tone-in-noise detection study to examine 2 psychoacoustical phenomena in rabbit and in human listeners: (a) the binaural masking level difference (BMLD) and (b) differential performance across reproducible noise masker waveforms. The rabbits demonstrated a BMLD comparable in size to other species. Significant differences in performance across reproducible noise masker waveforms were seen in the rabbits. This performance was compared with the performance of human listeners using the same set of waveforms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial auditory thalamic nuclei are necessary for eyeblink conditioning.

The auditory conditioned stimulus (CS) pathway that is necessary for delay eyeblink conditioning was investigated with induced lesions of the medial auditory thalamus contralateral to the trained eye in rats. Rats were given unilateral lesions of the medial auditory thalamus or a control surgery followed by twenty 100-trial sessions of delay eyeblink conditioning with a tone CS and then five sessions of delay conditioning with a light CS. Rats that had complete lesions of the contralateral medial auditory thalamic nuclei, including the medial division of the medial geniculate, suprageniculate, and posterior intralaminar nucleus, showed a severe deficit in conditioning with the tone CS. Rats with complete lesions also showed no cross-modal facilitation (savings) when switched to the light CS. The medial auditory thalamic nuclei may modulate activity in a short-latency auditory CS pathway or serve as part of a longer latency auditory CS pathway that is necessary for eyeblink conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the anterior cingulate cortex in the control over behavior by Pavlovian conditioned stimuli in rats.

To investigate the contribution of the anterior cingulate cortex (ACC) to stimulus-reward learning, rats with lesions of peri- and postgenual ACC were tested on a variety of Pavlovian conditioning tasks. Lesioned rats learned to approach a food alcove during a stimulus predicting food, and responded normally for conditioned reinforcement. They also exhibited normal conditioned freezing and Pavlovian-instrumental transfer, yet were impaired at autoshaping. To resolve this apparent discrepancy, a further task was developed in which approach to the food alcove was under the control of 2 stimuli, only 1 of which was followed by reward. Lesioned rats were impaired, approaching during both stimuli. It is suggested that the ACC is not critical for stimulus-reward learning per se, but is required to discriminate multiple stimuli on the basis of their association with reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal processing of information: The role of the medial prefrontal cortex and hippocampus: Theoretical comment on gilmartin and mcechron (2005).

M. R. Gilmartin and M. D. McEchron (2005) reported that single cells recorded in the prelimbic cortex of rats during the acquisition of trace fear conditioning display multiple patterns of neuronal firing during the trace. These finding are discussed in the context of the role of the prelimbic cortex in processing temporal information during trace conditioning and delayed matching- or nonmatching-to-sample paradigms based on both electrophysiology and lesion evidence. In addition, evidence is provided for a role of the hippocampus in supporting temporal processing of information and its potential interaction with the prelimbic cortex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of awareness in Pavlovian conditioning: Empirical evidence and theoretical implications.

This article reviews research over the past decade concerning the relationship between Pavlovian conditioning and conscious awareness. The review covers autonomic conditioning, conditioning with subliminal stimuli, eyeblink conditioning, conditioning in amnesia, evaluative conditioning, and conditioning under anesthesia. The bulk of the evidence is consistent with the position that awareness is necessary but not sufficient for conditioned performance, although studies suggestive of conditioning without awareness are identified as worthy of further investigation. Many studies have used inadequate measures of awareness, and strategies for increasing validity and sensitivity are discussed. It is concluded that conditioning may depend on the operation of a propositional system associated with consciousness rather than a separate, lower level system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the medial prefrontal cortex in acquired distinctiveness and equivalence of cues.

In the present study, the authors examined the role of the medial prefrontal cortex in acquired equivalence and distinctiveness of cues. Rats were placed in 4 experimental contexts (A, B, C, and D) where they received presentations of 2 auditory stimuli (X and Y). In Contexts A and B, X was paired with food and Y was not, whereas in Contexts C and D, Y was paired with food and X was not. Rats that received sham lesions and those with lesions of the medial prefrontal cortex acquired this configural discrimination equally readily. Rats then received many pellets in A but not in C. After this training, sham-lesion rats exhibited more magazine activity in B than in D (an acquired distinctiveness/acquired equivalence effect), whereas those with medial prefrontal cortex lesions did not. These results indicate that the medial prefrontal cortex is involved in the process by which experience with stimuli influences the degree of generalization between them. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Autonomic and eyeblink conditioning are closely related to contingency awareness: Reply to Wiens and ?hman (2002) and Manns et al (2002).

S. Wiens and A. Ohman (see record 2002-00340-002) disputed the conclusion that Pavlovian conditioning is strongly related to contingency awareness (P. F. Lovibond & D. R. Shanks, see record 2002-00340-001) on the basis that an inappropriate definition of awareness was used. J. R. Manns, R. E. Clark, and L. R. Squire (see record 2002-00340-003) contended that delay eyeblink conditioning is independent of awareness. The authors of the present article consider these arguments, highlight several problems in the new studies described by the commentators, and conclude that there is still little evidence for unconscious conditioning in either subliminal autonomic conditioning or eyeblink conditioning. The most parsimonious account of existing data is that a single learning process gives rise to both awareness and conditioned responding. Further progress in evaluating the possibility of unconscious conditioning would be facilitated by the development of more completely specified and testable dual-process models. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial prefrontal cortex lesions in the female rat affect sexual and maternal behavior and their sequential organization.

Temporal sequences of sexual and maternal behaviors in female rats and their correlation with each other and with performance on a sensory-motor gating response inhibition task assessed by prepulse inhibition (PPI) were investigated following medial prefrontal cortex (mPFC) lesions. Following excitotoxic mPFC (n = 10) or sham (n = 9) lesions, sexual behaviors across the ovarian cycle were scored. After mating and parturition, maternal interactions were scored until pups reached postnatal Day 10. After resumption of the ovarian cycle, the female rats were tested for PPI. Compared with sham lesions, mPFC lesions impaired proceptive behaviors and some maternal behaviors (e.g., pup retrieval, pup licking) but did not affect others (e.g., nest building, pup mouthing). Lesions disrupted temporal sequences of solicitations (number of male orientations followed, within 4 s, by a level change) and pup retrievals (number of pup retrievals followed, within 5 s, by another retrieval). These sequential behavior patterns were significantly correlated with each other and with PPI. However, when PPI effects were partialled out, group differences were less strong, but persisted. This study demonstrated that mPFC manipulations affect actions rich in sequential structure in response to biologically relevant stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Unblocking in Pavlovian fear conditioning.

Six experiments used rats to study blocking and unblocking of fear learning. An excitatory stimulus (A) blocked fear learning to a neutral stimulus (B). Unblocking of B occurred if the AB compound signaled an increase in unconditioned stimulus (US) intensity or number. Assessments of associative change during blocking showed that more was learned about B than A. Such assessments during unblocking revealed that more was learned about B than A following an increase in US intensity but not US number. These US manipulations had no differential effects on single-cue learning. The results show that variations in US intensity or number produce unblocking of fear learning, but for each there is a different profile of associative change and a potentially different mechanism. (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)     

Perirhinal cortex lesions impair simultaneous but not serial feature-positive discrimination learning.

The role of the perirhinal cortex in discriminative eyeblink conditioning was examined by means of feature-positive discrimination procedures with simultaneous (A-/XA+) and serial (A-/X→A+) stimulus compounds. Lesions of the perirhinal cortex severely impaired acquisition of simultaneous feature-positive discrimination but produced no impairment in serial feature-positive discrimination. The results suggest that the perirhinal cortex plays a role in discriminative eyeblink conditioning by resolving ambiguity in discriminations with overlapping stimulus elements. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional modularity of the medial prefrontal cortex: Involvement in human empathy.

To investigate medial frontal lobe mediation of human empathy, the authors analyzed the activation areas in statistical parametric maps of 80 studies reporting neural correlates of empathic processing. The meta-analysis revealed 6 spatially distinct activation clusters in the medial part of the frontal lobe dorsal to the intercommissural plane. The most dorsal cluster coincided with the left supplementary motor area (SMA). Rostrally adjacent was a cluster that overlapped with the right pre-SMA. In addition, there were 3 left-hemispheric and 1 right-hemispheric clusters located at the border between the superior frontal and anterior cingulate gyrus. A broad spectrum of cognitive functions were associated with these clusters, including attention to one's own action, which was related to activations in the SMA, and valuation of other people's behavior and ethical categories, which was related to activations in the most rostroventral cluster. These data complement the consistent observation that lesions of the medial prefrontal cortex interfere with a patient's perception of own bodily state, emotional judgments, and spontaneous behavior. The results of the current meta-analysis suggest the medial prefrontal cortex mediates human empathy by virtue of a number of distinctive processing nodes. In this way, the authors' findings suggest differentiated aspects of self-control of behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)