Discriminative stimulus effects of diazepam and buspirone in normal volunteers.

A within-subject design was used to characterize the effects of dose manipulations on discriminative and self-reported effects of oral diazepam and buspirone. Subjects were trained to discriminate diazepam (10 mg) versus placebo (n = 10), or buspirone (10 or 15 mg) versus placebo (n = 9). The compounds were identified to subjects by letter code before discrimination training began. In later sessions, correct identifications at 2 hr after the oral administration of drug earned money. All subjects showed accurate discrimination performance during the test-of-acquisition phase. In a low-dose generalization phase, diazepam and buspirone produced dose-related increases in drug identifications across a four-fold range of doses. In a subsequent low-dose training phase, in which subjects were trained to discriminate progressively lower drug doses, the median lowest discriminable dose of diazepam and buspirone was 2.5 and 7.5 mg, respectively. Dose-response functions for drug identifications were shifted leftward in the low-dose training phase relative to the low-dose generalization phase, suggesting that reinforcement of progressively lower doses enhances drug discriminability. The self-reported effects of diazepam and buspirone were similar (e.g., both drugs increased ratings of drug strength and clumsy/uncoordinated) and different (e.g., diazepam but not buspirone increased ratings of drowsy/sleepy; buspirone but not diazepam increased ratings of tense/nervous). This study demonstrates discriminative and self-reported effects of diazepam and buspirone at doses lower than previously shown to be behaviorally active, and suggests that at commonly used clinical doses, diazepam is relatively more discriminable than buspirone.     

Aversive and appetitive electrodermal classical conditioning using pictures as stimuli

The principal goal of this study was to verify whether it was possible to obtain both aversive and appetitive electrodermal classical conditioning, using pictures as conditioned stimuli (CS), and unconditioned stimuli (US). Additionally, we tried to verify whether, as a consequence of such conditioning, diminution of the unconditioned response (UR) was observed. With this aim, IAPS (?International Affective Picture System?) pictures were selected as stimuli. A picture showing a burnt face was used as the aversive US (USav), and a picture showing a scene with erotic content was used as the appetitive US (USap). As the aversive CS (CSav), and appetitive CS (CSap), two images with intermediate values of valence and arousal showing male faces were selected. In the experimental group, 10 CSav/USav and 10 CSap/USap trials were presented. In the control group 10 CSav, CSap, USav, and USap trials were presented in pseudorandom order. Skin conductance response (SCR) elicited by both the CSs and the USs was scored. Results showed aversive conditioning, but neither appetitive conditioning nor UR diminution. Problems to obtain conditioning using pictures as stimuli and possible options to overcome them in future research are discussed.     

A comparison of classical eyelid conditioning in adults and infants

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

Emotional modulation of attention orienting: A classical conditioning study

Emotional modulation of attention shifting was investigated in Posner's (1980) spatial orienting task by conditioning the attention cue to an aversive white noise. Prior to the attention task, the Conditioning group received a 90dB white noise unconditioned stimulus (UCS) contingent upon the frame-lit rectangle attention cue, while the Control group received non-contingent presentations. The Conditioning group evidenced greater skin conductance responses to the frame-lit rectangle in the conditioning phase, reflecting an electrodermal conditioned response. In the attention phase, the frame-lit rectangle served as the attention cue in the spatial orienting task. The Conditioning group showed equally fast reaction times (RTs) to targets presented outside the location of the cue as to targets at the same location as the cue, reflecting elimination of the cognitive cost usually involved in shifting attention. The Control group evidenced the regular cost of shifting attention away from the location of the cue. The Conditioning group also evidenced a larger N1-component with a parietal distribution of the event-related brain potentials to the cue and a larger N1-component at the frontal regions to targets presented outside the cued location. This suggests that both visual orienting to the cue and attention shifting from cue to target on invalid trials were amplified by the emotional salience attached to the cue through the classical conditioning procedure.     

Constraint, alcoholism, and electrodermal response in aversive classical conditioning and mismatch novelty paradigms

This study investigated whether low levels of the personality trait of constraint and early-onset alcoholism would be associated with deficits in aversive conditioning and smaller responses to novelty in a stimulus mismatch protocol. Personality traits (constraint and socialization) and skin conductance responses (SCRs) during conditioning and novelty paradigms were assessed in alcoholics (n=41) and non-alcoholics (n=32). The conditioning protocol involved measuring SCRs after conditioned stimuli (CS+: tones) paired with shock, CS− tones unpaired with shock, and CS+ probes unpaired with shock. The mismatch protocol involved measuring SCRs to auditory stimuli consisting of a series of 5 pure tones of the same pitch followed a shorter white noise stimulus (the novel stimulus). Contrary to the hypothesis, alcoholics did not differ from non-alcoholics in SCRs to CS+ probes or on the mismatch measure (SCR novel tone—SCR to 5^th tone). Higher levels of constraint and self-reports of fear during conditioning were associated with smaller responses to both the CS+ probes and the CS− tones as well as the mismatch measure within non-alcoholics, but not within alcoholics. In alcoholics, low constraint was associated with greater habituation to CS+ probes, and poor differential conditioning on measures of change across trials in SCR to CS+ probes and CS− stimuli. The results suggest that different processes influence levels of constraint in non-alcoholics and alcoholics. The data indicate that low constraint in non-alcoholics is associated with allocating fewer processing resources to potentially significant stimuli, rather than being associated with a specific deficit in aversive conditioning per se.     

Expectancy-learning and evaluative learning in human classical conditioning: affective priming as an indirect and unobtrusive measure of conditioned stimulus valence

It has been argued that in classical conditioning two processes might be operative. First, one may learn that the conditioned stimulus (CS+) is a valid predictor for the occurrence of the biologically negative or positive event (US; expectancy-learning). Second, one may learn to perceive the conditioned stimulus itself as a negative or positive stimulus, depending on the valence of the event it has been associated with (evaluative learning). Until the present, however, both forms of learning have been investigated using rather different conditioning procedures. Using a differential aversive conditioning preparation with pictures of human faces as CSs and an electrocutaneous stimulus as US, we were able to demonstrate that both forms of learning can co-occur. Moreover, the extent of evaluative learning in this aversive conditioning procedure did not significantly differ from the amount of evaluative learning in an evaluative conditioning procedure with positive and negative adjectives as USs, which was administered to the same participants. In the present study evaluative learning was not only indexed by direct evaluative ratings, but we introduced affective priming as an indirect and unobtrusive, reaction time based measure of stimulus valence. Finally, imagery instructions during acquisition did not facilitate expectancy-learning nor evaluative learning.     

Pentylenetetrazole as an unconditioned stimulus for olfactory and contextual fear conditioning in rats

The association of five footshocks with a neutral odor is able to establish an olfactory fear conditioning in rats. The present study sought to investigate whether the systemic administration of pentylenetetrazole (PTZ; 3.75–15 mg/kg) would turn the coffee odor in a conditioned stimulus in the fear conditioning paradigm. The results showed that rats started to display risk assessment and avoidance after PTZ (15 mg/kg)–coffee odor pairing. When three mild footshocks (0.4 mA for 2 s) were delivered during this pairing, the conditioned response exhibited was greater than before. In both cases, however, pretreatment with the benzodiazepine midazolam (MDZ. 0.5 mg/kg i.p.) fully counteracted the expression of these defensive behaviors. Moreover, after being paired with 15 mg/kg of PTZ alone or combined with footshocks, the coffee odor was able to promote a new fear conditioning related to the context where it was re-exposed. The present findings point out the usefulness of PTZ as an unconditioned stimulus to promote fear conditioning to olfactory and contextual cues in rats.     

Food delivery as a conditional stimulus: Feature-learning and memory in pigeons

Three experiments investigated the learning and memory of discriminations based on presence versus absence of a pre-trial food delivery. In Experiment 1 half the illuminations of a response key were followed by food regardless of the subject's behavior. In one group an extra food delivery preceded only reinforced trials (feature-positive condition), whereas in a second group it preceded only nonreinforced trials (feature-negative condition). Key pecks and approaches revealed more rapid and superior discrimination learning in the first group. Experiment 2 replicated the results of Experiment 1 but yielded no evidence that greater “unexpectedness” of pretrial food conditions facilitates discriminative performance. In Experiment 3, individual pigeons trained on a conditional discrimination exhibited a within-subject feature-positive superiority. Delay between pretrial and trial stimuli interacted with feature-positive versus feature-negative training in both the between-group (Experiment 2) and within-subject (Experiment 3) procedures: performance was decremented at both short and long delays in the feature-positive condition but was decremented only at longer delays in the feature-negative condition. The feature-positive superiority obtained here is incompatible with explanations based on either the general concept of “perceptual organization” or on the conditional nature of feature-negative discriminations.     

Unique characteristics of neonatal classical conditioning: The role of the amygdala and locus coeruleus

The central nervous system of altricial infants is specialized for optimizing attachments to their caregiver. During the first postnatal days, infant rats show a sensitive period for learning and particularly susceptible to learning an attraction to their mother’s odor. Classical conditioning appears to underlie this learning that is expressed behaviorally as anincreased ability to acquire odor preferences and a decreased ability to acquire odor aversions. Specifically, in neonatal rats, pairing an odor with moderately painful shock (0.5mA) or milk produces a subsequent relativepreference for that odor. The neural circuitry supporting theincreased ability to acquire odor preferences appears to be the heightened functioning of the noradrenergic pontine nucleus locus coeruleus. Indeed, norepinephrine from the locus coeruleus appears to be both necessary and sufficient for learning during the sensitive period. On the other hand, thedecreased ability to acquire odor aversions seems to be due to the lack of participation of the amygdala in at least some aversive learning situations. The site of plasticity in the pup’s brain appears to be limited to the olfactory bulb. This neonatal sensitive period for learning ends around postnatal day 9–10, at which time pups make the transition from crawling to walking and classical conditioning becomes “adultlike”. The neonatal behavioral and neural induced changes are retained into adulthood where it modifies sexual behavior.     

Neuroscience and learning: lessons from studying the involvement of a region of cerebellar cortex in eyeblink classical conditioning

How the nervous system encodes learning and memory processes has interested researchers for 100 years. Over this span of time, a number of basic neuroscience methods has been developed to explore the relationship between learning and the brain, including brain lesion, stimulation, pharmacology, anatomy, imaging, and recording techniques. In this paper, we summarize how different research approaches can be employed to generate converging data that speak to how structures and systems in the brain are involved in simple associative learning. To accomplish this, we review data regarding the involvement of a particular region of cerebellar cortex (Larsell's lobule HVI) in the widely used paradigm of classical eyeblink conditioning. We also present new data on the role of lobule HVI in eyeblink conditioning generated by combining temporary brain inactivation and single-cell recording methods, an approach that looks promising for further advancing our understanding of relationships between brain and behavior.     

Post-extinction conditional stimulus valence predicts reinstatement fear: Relevance for long-term outcomes of exposure therapy

Exposure therapy for anxiety disorders is translated from fear conditioning and extinction. While exposure therapy is effective in treating anxiety, fear sometimes returns after exposure. One pathway for return of fear is reinstatement: unsignaled unconditional stimuli following completion of extinction. The present study investigated the extent to which valence of the conditional stimulus (CS+) after extinction predicts return of CS+ fear after reinstatement. Participants (N = 84) engaged in a differential fear conditioning paradigm and were randomised to reinstatement or non-reinstatement. We hypothesised that more negative post-extinction CS+ valence would predict higher CS+ fear after reinstatement relative to non-reinstatement and relative to extinction retest. Results supported the hypotheses and suggest that strategies designed to decrease negative valence of the CS+ may reduce the return of fear via reinstatement following exposure therapy.     

The effects of lesions in the central nucleus of the amygdala on appetitive classical conditioning in rats

Abstract: Lesions in the central nucleus of the amygdala (cAMY) have been known to interfere with the acquisition of fear classical conditioning when footshock is used as an unconditioned stimulus (US). The present study examined whether or not a similar interference would occur with an appetitive US. Five rats with lesions in the cAMY (the cAMY group), and eight unoperated control rats were trained in an appetitive classical conditioning paradigm, which did not include elements of operant learning, using a visual conditioned stimulus (CS) (5 W of light for 10 s duration) paired with a food pellet US (45 mg, cheese flavor). The behavioral index of appetitive conditioning was an increase in rearing approach behavior to the CS after CS and US pairings. During CS and US pairings, the movement of the rat was limited so that this approach behavior could not occur. As a result, all control rats showed an increase in rearing, but the cAMY group did not. These results suggest that the cAMY is critical for appetitive as well as fear classical conditioning.     

Stimulus- and response-reinforcer contingencies in autoshaping, operant, classical, and omission training procedures in rats

Separate groups of rats received 500 trials of lever-press training under autoshaping (food delivery followed 10-second lever presentations, or occurred immediately following a response); operant conditioning (responding was necessary for food delivery); and classical conditioning (food followed lever presentations regardless of responding). Each group then received 500 trials on an omission procedure in which food was omitted on trials with a response. Another group received 1000 trials on the omission procedure, and a fifth group, random control, received 1000 uncorrelated presentations of lever and food. The autoshaping, operant, and classical groups reached high response levels by the end of initial training. Acquisition was fastest in the autoshaping group. Responding remained consistently low in the control group. The omission group responded at a level between the control group and the other three groups. During omission training, responding in these three groups declined to the omission-group level. During omission training, the rats continued contacting the lever frequently after lever pressing had declined. Response maintenance under omission training seems not to require topographic similarity between the response and reinforcer-elicited consummatory behaviors.     

Exploring classical conditioning for strengthening the links between semantic and lexical representations in pure anomia: Preliminary findings from a single case study

The same language symptom might arise at different functional loci in people with aphasia. Therefore, it is plausible that different therapeutic interventions should be adopted to approach the same difficulties in different patients. Although this point of view is still widely accepted, recently the focus has shifted from the functional locus of a rehabilitative intervention to the mechanisms of action underlying the relearning process. We maintain that both aspects should be taken into account when programming a rehabilitative intervention; furthermore, investigating relearning mechanisms might shed new light on the functional architecture of the disrupted processes. Here, we investigated, in a single case study, whether classical conditioning was a suitable relearning paradigm for targeting word‐finding difficulties in pure anomia, that is in a patient with an impairment in accessing intact output lexical representations from a spared semantic system. Using a word‐repetition task on picture presentation, we contrasted a condition in which the stimulus onset asynchrony between word and picture stimuli was well suited to produce classical conditioning with a condition in which repetition training could not benefit from this learning mechanism. Only classical conditioning training exerted a significant, long‐lasting effect on our patient's naming skill. Tentative implications of our results for the functional architecture of single‐word processing are discussed.     

Naming in conditional discrimination and stimulus equivalence.

Using a matching-to-sample procedure, McIntire, Cleary, and Thompson (1987) taught monkeys the conditional relations A1-R1-A1-R1, A2-R2-A2-R2, A1-R1-B1-R1, A2-R2-B2-R2, B1-R1-C1-R1, and B2-R2-C2-R2, where the first and third terms in each relation refer to the sample and comparison stimuli, respectively, and the second and last terms refer to the emission of a distinctive pattern of responding. The subjects were then tested for the emergent relations A-C, C-A, B-A, C-B, and B-B, with the differential response produced by a given stimulus during training also emitted on test trials (e.g., A1-R1-C1-R1). The performances of both subjects were as accurate on the tested relations as they had been on the trained relations. The new relations were characterized as demonstrations of stimulus equivalence. However, the conditional discrimination literature shows that such training procedures generate control of comparison selection by the differential response patterns. Therefore, no emergent relations were demonstrated because all of the trained response-stimulus relations were preserved on test trials. This paper suggests that these procedures do not provide an appropriate analogy for the kind of emergent stimulus-stimulus relations exhibited by human subjects in equivalence studies and outlines a paradigm for assessing the relative influence of stimulus-stimulus and response-stimulus relations.     

Drug discrimination: stimulus control during repeated testing in extinction

Rats were trained, under a two-lever drug-discrimination procedure, to respond differentially depending upon whether lorazepam (1.0 mg/kg) or no injection had been administered before the session. Responses on the appropriate lever produced a food pellet under a modified fixed-ratio (FR) 10 schedule, in which the 10 responses had to be emitted consecutively. In reinforcement tests, completing an FR 10 on either lever produced a pellet. In extinction tests, stimulus changes paired with reinforcement occurred but no pellet was delivered. Training sessions were conducted between test sessions. Each of four extinction phases consisted of six tests preceded by one stimulus (e.g., lorazepam). Repeated exposures to extinction reduced response rates for all rats, but stimulus control, as inferred from either percentage of total responses or percentage of total FR 10s on the drug-appropriate lever, remained high. The percentage of total FR 10s measure was less subject to skewing under low-rate conditions than was the percentage of total responses measure and provided an evaluation of stimulus control in terms of meeting the consecutive response contingency. These results demonstrate a level of independence between response rate and stimulus control in drug discrimination, which has positive implications for the validity of interpreting discriminative effects of novel test conditions in well-trained animals, even when overall response rates are low.     

Simple and conditional visual discrimination with wheel running as reinforcement in rats.

Three experiments explored whether access to wheel running is sufficient as reinforcement to establish and maintain simple and conditional visual discriminations in nondeprived rats. In Experiment 1, 2 rats learned to press a lit key to produce access to running; responding was virtually absent when the key was dark, but latencies to respond were longer than for customary food and water reinforcers. Increases in the intertrial interval did not improve the discrimination performance. In Experiment 2, 3 rats acquired a go-left/go-right discrimination with a trial-initiating response and reached an accuracy that exceeded 80%; when two keys showed a steady light, pressing the left key produced access to running whereas pressing the right key produced access to running when both keys showed blinking light. Latencies to respond to the lights shortened when the trial-initiation response was introduced and became much shorter than in Experiment 1. In Experiment 3, 1 rat acquired a conditional discrimination task (matching to sample) with steady versus blinking lights at an accuracy exceeding 80%. A trial-initiation response allowed self-paced trials as in Experiment 2. When the rat was exposed to the task for 19 successive 24-hr periods with access to food and water, the discrimination performance settled in a typical circadian pattern and peak accuracy exceeded 90%. When the trial-initiation response was under extinction, without access to running, the circadian activity pattern determined the time of spontaneous recovery. The experiments demonstrate that wheel-running reinforcement can be used to establish and maintain simple and conditional visual discriminations in nondeprived rats.     

Fear conditioning and extinction in anxiety- and depression-prone persons

Anxiety and depression frequently co-occur and may share similar deficits in the processing of emotional stimuli. High anxiety is associated with a failure in the acquisition and extinction of fear conditioning. Despite the supposed common deficits, no research has been conducted on fear acquisition and extinction in depression. The main aim of the present study was to investigate and compare fear acquisition and extinction in anxiety- and depression-prone participants. Non-clinical anxious, depressive, anxious-depressive and control participants performed a fear discrimination task. During acquisition, the CS+ predicted an aversive event (unconditioned stimulus, US) and the CS? safety (no US). During extinction, the CS+ was no longer followed by the US, rendering it (temporarily) into a safety signal. On each CS participants rated their US expectancy; skin conductance responses (SCRs) were measured throughout. The expectancy scores indicated that high anxiety resulted in less safety learning during acquisition and extinction; no effect of depression was observed. SCRs showed that high-anxiety persons displayed less discrimination learning (CS+ minus CS?) during acquisition than low-anxiety persons. During extinction, high-depression persons demonstrated more discriminative SCR than low-depression persons. The observed discrepancies in response patterns of high-anxiety and -depression persons seem to indicate distinctive information processing of emotional stimuli.     

Incongruous stimulus pairing and conditional discrimination training: effects on relational responding

In Experiment 1, 5 subjects were exposed to a stimulus-pairing procedure in which two nonsense syllables, identified by a letter-number code as A1 and C2, each predicted the onset of a sexual film clip, and the nonsense syllables A2 and C1 each predicted the onset of a nonsexual film clip. Subjects were then exposed to a matching-to-sample test in which the nonsense syllables A1 and A2 were presented as sample stimuli and C1 and C2 were presented as comparison stimuli and vice versa (i.e., C stimuli as samples and A stimuli as comparisons). All subjects matched A1 with C2 and A2 with C1. Subjects were then trained on the conditional discriminations A1-B1, A2-B2, B1-C1, B2-C2, after which the matching-to-sample test was again administered. All subjects continued to match A1 with C2 and A2 with C1 in accordance with the earlier stimulus-pairing contingencies. An additional 5 subjects were exposed first to conditional discrimination training and testing before being exposed to the incongruous stimulus pairing and matching-to-sample testing. Under these conditions, 4 of the 5 subjects always matched A1 with C1 and A2 with C2. Experiment 2 replicated Experiment 1, except that a matching-to-sample test was not administered following the initial training procedure. Under these conditions, matching-to-sample test performances were controlled by the contingencies that had immediately preceded the test. Experiment 3 indicated that initial matching-to-sample test performances were unlikely to change, even after repeated exposure to incongruous training and testing. Experiment 4 demonstrated that pretraining with unrelated stimulus sets increased the sensitivity of matching-to-sample test performances to incongruous contingencies when they were similar in format to those arranged during pretraining. These data may have implications for a behavior-analytic interpretation of attitude formation and change.     

Bilaterally recorded multiple-unit activity of the cingulate cortex during head turning conditioning with unilateral medial forebrain bundle stimulation

Cats were conditioned to turn their heads using a tone conditioned stimulus (CS) and medial forebrain bundle stimulation (MFB) unconditioned stimulus (US). The CS+ was delivered to one ear at a time, in random order, followed by the US. A tone of a different frequency was used as a CS-. The cats learned to respond differentially to the CSs showing head movements of greater acceleration to the CS+ than CS- over sessions. Bilateral recordings of cingulate cortex multiple-unit activity showed increased response amplitudes over sessions and larger responses in the hemisphere ipsilateral to the US. Since ipsilateral multiple-unit responses did not differ for the CSs, the asymmetry was probably due to the sensitizing effect of the unilateral US. Although increases in cingulate cortex neural activity coincided with increases in conditioned head movements, larger activation of the cingulate cortex ipsilateral to the US suggests that the neural changes were independent of these movements.