Correction to Fortier et al. (2008).

Reports an error in "Delay discrimination and reversal eyeblink classical conditioning in abstinent chronic alcoholics" by Catherine Brawn Fortier, Elizabeth M. Steffen, Ginette LaFleche, Jonathan R. Venne, John F. Disterhoft and Regina E. McGlinchey (Neuropsychology, 2008[Mar], Vol 22[2], 196-208). 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. (The following abstract of the original article appeared in record 2008-02526-007.) 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)     

Large-scale functional connectivity in associative learning: interrelations of the rat auditory, visual, and limbic systems

Large-scale functional connectivity in associative learning: interrelations of the rat auditory, visual, and limbic systems. J. Neurophysiol. 80: 3148-3162, 1998. Functional relations between specialized parts of the brain may be important determinants of learned behaviors. To study this, we examined the interrelations of the auditory system with several extraauditory structures in two groups of rats having different behavioral histories. Both groups were trained to associate a tone conditional stimulus (CS) with an aversive unconditional stimulus (US). For one group, a light presented with the tone predicted the absence of the US (group TL-). In the other group, the light was a neutral stimulus (group TL0). Fluorodeoxyglucose (FDG) incorporation was measured in the presence of the tone-light compound. Because the tone-light compound was physically identical for both groups, neural differences between groups reflected differences in the learned associative properties of the stimuli. Covariances of FDG uptake in the auditory system and extraauditory structures were examined using partial least squares. Three strong covariance or functional connectivity patterns were identified. The first pattern mainly reflected similarities between groups, with strong interrelations between the subcortical auditory system and the thalamocortical visual system, cerebellum, deep cerebellar nuclei, and midline thalamus. This pattern of interactions may represent part of a common circuit for relaying the associative value of the tone CS to the cerebellum and the midline thalamus. The external nucleus of the inferior colliculus and medial division of the medial geniculate nucleus were associated more strongly with this pattern for group TL-, which was interpreted as representing the change of the associative value of the tone by the light, mediated through extraauditory influences on these two regions. A second pattern involved midbrain auditory regions, superior colliculus, zona incerta, and subiculum and was stronger for group TL0. The relations between midbrain structures may represent the excitatory conditioned response (CR) evoked by the tone in this group. The final pattern was strongest in group TL- and involved interrelations of the thalamocortical auditory system with hippocampus, basolateral amygdala, and hypothalamus. This pattern may represent the learned inhibition of the CR to the tone in the presence of the light. These findings are consistent with behavioral studies suggesting that at least two types of associations are formed during associative learning. One is the sensory relation of the stimuli and another is the relation between the CS and the affective components of the US. These behavioral associations are mapped to the patterns of functional connectivity between auditory and extraauditory regions.     

Taste-potentiated odor aversion learning: Role of the amygdaloid basolateral complex and central nucleus.

Examined the relative contributions of the amygdaloid basolateral complex (ABL) and central nucleus (CN) to taste-potentiated odor aversion (TPOA) learning, an associative learning task that is dependent on information processing in 2 sensory modalities. In Exp 1, rats with neurotoxic lesions of these systems were trained on the TPOA task by presenting a compound taste–odor conditioned stimulus (CS), which was followed by LiCl administration. Results showed that ABL damage caused an impairment in potentiated odor aversion learning but no deficit in the conditioned taste aversion. In contrast, rats with CN damage learned both tasks. Exp 2 examined the effects of ABL damage on TPOA and odor discrimination learning. The odor discrimination procedure used a place preference task to demonstrate normal processing of olfactory information. Results indicated that although ABL-lesioned animals were impaired on TPOA, there was no deficit in odor discrimination learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Classical conditioning modifies cytochrome oxidase activity in the auditory system

The effects of excitatory classical conditioning on cytochrome oxidase activity in the central auditory system were investigated using quantitative histochemistry. Rats in the conditioned group were trained with consistent pairings of a compound conditional stimulus (a tone and a light) with a mild footshock, to elicit conditioned suppression of drinking. Rats in the pseudorandom group were exposed to pseudorandom presentations of the same tone, light and shock stimuli without consistent pairings. Untrained rats in a naive group did not receive presentations of the experimental stimuli. The findings demonstrated that auditory fear conditioning modifies the metabolic neuronal responses of the auditory system, supporting the hypothesis that sensory neurons are responsive to behavioural stimulus properties acquired by learning. There was a clear distinction between thalamocortical and lower divisions of the auditory system based on the differences in metabolic activity evoked by classical conditioning, which lead to an overt learned behavioural response versus pseudorandom stimulus presentations, which lead to behavioural habituation. Increases in cytochrome oxidase activity indicated that tone processing is enhanced during associative conditioning at upper auditory structures (medial geniculate nucleus and secondary auditory cortices). In contrast, metabolic activation of lower auditory structures (cochlear nuclei and inferior colliculus) in response to the pseudorandom presentation of the experimental stimuli suggest that these areas may be activated during habituation to tone stimuli. Together these findings show that mapping the metabolic activity of cytochrome oxidase with quantitative histochemistry can be successfully used to map regional long-lasting effects of learning on brain systems.     

Induction of receptive field plasticity in the auditory cortex of the guinea pig during instrumental avoidance conditioning.

Classical tone conditioning shifts frequency tuning in the auditory cortex to favor processing of the conditioned stimulus (CS) frequency versus other frequencies. This receptive field (RF) plasticity is associative, highly specific, rapidly acquired, and indefinitely retained—all important characteristics of memory. The investigators determined whether RF plasticity also develops during instrumental learning. RFs were obtained before and up to 24 hr after 1 session of successful 1-tone avoidance conditioning in guinea pigs. Long-term RF plasticity developed in all subjects (N?=?6). Two-tone discrimination training also produced RF plasticity, like classical conditioning. Because avoidance responses prevent full elicitation of fear by the CS, long-term RF plasticity does not require the continual evocation of fear, suggesting that neural substrates of fear expression are not essential to RF plasticity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Basal forebrain stimulation induces discriminative receptive field plasticity in the auditory cortex.

Learning alters receptive field (RF) tuning in the primary auditory cortex (ACx) to emphasize the frequency of a tonal conditioned stimulus. RF plasticity is a candidate substrate of memory, as it is associative, specific, discriminative, rapidly induced, and enduring. The authors hypothesized that it is produced by the release of acetylcholine in the ACx from the basal forebrain (BasF), caused by presentation of reinforced but not nonreinforced conditioned stimuli. Waking adult male Hartley guinea pigs (n?=?16) received 1 of 2 tones followed by BasF stimulation, in a single session of 30 pseudo-random order trials each. RFs from neuronal discharges before and after differential pairing revealed the induction of predicted plasticity, as well as increased responses to the paired tone and decreased responses to the unpaired tone. Thus, highly specific, learning-induced RF plasticity in the ACx may be produced by activation of the BasF by a reinforced conditioned stimulus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Arousal-related associative response characteristics of dorsal lateral geniculate nucleus neurons during acoustic Pavlovian fear conditioning.

This research determined whether fear-conditioned, acoustic stimuli induce thalamic arousal reflected in associative responses in dorsal lateral geniculate nucleus (dLGN) neurons. Rabbits received a Pavlovian discriminative fear conditioning procedure in which one tone conditioned stimulus (CS+) was always paired with an aversive unconditioned stimulus (UCS) and another tone (CS–) was never paired with the UCS. Responses of single dLGN neurons to random CS+ and CS– presentations were then recorded. Nine of 15 recorded neurons demonstrated significantly greater firing during the CS+ versus the CS–. Their spontaneous activity demonstrated tonic firing during increased neocortical arousal and burst firing during decreased neocortical arousal. The results demonstrate that dLGN neurons show associative responses to fear-conditioned, acoustic stimuli and present a model for investigating the neural circuits by which such stimuli affect sensory processing at the thalamic level. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Risk for alcoholism and classical conditioning to signals for punishment: Evidence for a weak behavioral inhibition system.

Nonalcoholic men with high-density family histories of alcohol dependence (high risk) were compared with men with negative family histories (low risk) on a differential classical conditioning protocol that examined the acquisition of conditioned skin conductance responses (SCRs) to a tone (CS+) signaling the occurrence of an electric shock. High-risk Ss had significantly smaller SCRs to the CS+ tone probes during the acquisition phase and poor response discrimination between CS+ probes and CS– tones that were not paired with shock. The low-risk Ss showed a consistent pattern of discrimination between the CS+ and CS– tones. Unresponsivity to the CS+ probes was significantly related to more alcohol-related problems. The results suggest a relationship between risk for alcohol abuse and poor conditioning to signals for punishment, possibly reflecting weak behavioral inhibition system processes (D. C. Fowles; 1987). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nicotinic cholinergic system involvement in eyeblink classical conditioning in rabbits.

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

Reassessment of socially mediated learning in Siamese fighting fish (Betta splendens).

Seven experiments examined a previous report of Pavlovian conditioning of territorial behavior using a mirror unconditioned stimulus/stimuli (UCS) in Betta splendens. Control procedures omitted from the original research were included. Three studies failed to find that exposure to a mirror (UCS) in a colored tunnel conditioned stimulus/stimuli (CS+) produces learned approach to this tunnel. Instead, the fish exhibited unlearned green color preferences prior to mirror exposure and highly variable, random tunnel preferences after mirror exposure, One experiment provided evidence for an associative effect with the red CS+, but training with the green CS+ did not produce enhanced tunnel preferences. In contrast, spatial discrimination was shown in 2 experiments. The data, taken with other failures to replicate, raised questions about the biological preparedness of B. splendens to learn to associate agonistic responses with color features in the environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Associative learning modifies the shortening reflex in the semi-intact leech Hirudo medicinalis: Effects of pairing, predictability, and CS preexposure.

Three experiments addressed the importance of the inter-event relationships of contiguity and contingency for associative learning in the semi-intact leech. It was found that both of these relationships are important for the leech to acquire a learned association between a CS (touch) and unconditioned stimulus (UCS; shock). The learning can be extinguished if training is followed by explicitly unpaired presentations of the CS and UCS, which removes the contiguity between the stimuli. Learning is degraded by the introduction of unpredicted UCSs, as well as by unreinforced presentations of the CS (CS preexposure); both manipulations reduce the contingency between the CS and UCS. These results suggest that the associative process in both vertebrates and invertebrates share considerable functional similarity in the inter-event relationships important to learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cerebellar stimulation as an unconditioned stimulus in classical conditioning.

Implanted rabbits with chronic stimulating electrodes in white matter underlying lobule HVI of the cerebellar cortex. Stimulation elicited movements of the face or neck and, when paired with a tone CS, produced learning comparable to that seen with peripheral unconditioned stimulus/stimuli (UCS). CS-alone trials produced extinction. Reinstatement of paired trials produced reacquisition with savings. Additional groups received either explicitly or randomly unpaired CS–UCS trials before paired conditioning. Low-frequency responding during these sessions indicated that the paired training results were associative and not due to pseudoconditioning or sensitization. Explicitly unpaired sessions retarded learning on subsequent paired trials compared with groups that received either randomly unpaired or no CS–UCS preexposure. These results are interpreted in terms of the role of the cerebellum and associated pathways in classical conditioning of motor responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intertrial interval as a contextual stimulus: Further analysis of a novel asymmetry in temporal discrimination learning.

Four experiments investigated discrimination learning when the duration of the intertrial interval (ITI) signaled whether or not the next conditional stimulus (CS) would be paired with food pellets. Rats received presentations of a 10-s CS separated half the time by long ITIs and half the time by short ITIs. When the long ITI signaled that the CS would be reinforced and the short interval signaled that it would not be (Long+/Short?), rats learned the discrimination readily. However, when the short ITI signaled that the CS would be reinforced and the long interval signaled that it would not (Short+/Long?), discrimination learning was much slower. Experiment 1 compared Long+/Short? and Short+/Long? discrimination learning with 16-min/4-min or 4-min/1-min ITI combinations. Experiment 2 found no evidence that Short+/Long? learning is inferior because the temporal cue corresponding to the short interval is ambiguous. Experiment 3 found no evidence that Short+/Long? learning is poor because the end of a long ITI signals a substantial reduction in delay to the next reinforcer. Long+/Short? learning may be faster than Short+/Long?because elapsing time involves exposure to a sequence of hypothetical stimulus elements (e.g., A then B), and feature-positive discriminations (AB+/A?) are learned quicker than feature-negative discriminations (A+/AB?). Consistent with this view, Experiment 4 found a robust feature-positive effect when sequentially presented CSs played the role of elements A and B. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditional stimulus probability and activity of hippocampal, cingulate cortical, and limbic thalamic neurons during avoidance conditioning in rabbits.

Multi-unit and field potential responses in the anterior (AC) and posterior cingulate cortices (PC), dentate gyrus (DG), and anterior ventral (AV) and medial dorsal (MD) thalamic nuclei of rabbits were recorded during acquisition and performance of a locomotor conditioned response (CR). The CR, stepping in an activity wheel in response to a tone (conditioned stimulus [CS+]), prevented the occurrence of a shock unconditioned stimulus (UCS) scheduled 5 sec after CS+ onset. Ss also learned to ignore a different tone (CS–), not predictive of the UCS. Training was given daily until behavioral discrimination reached criterion. After criterion, asymmetric probability (AP) sessions were given that were the same as the conditioning session except for probability manipulation. A significant discriminative response developed in all regions during behavioral acquisition. The unit response in the AP session was enhanced in all areas by rare presentation of the CS–, compared with the equal and frequent CS– conditions. Rare presentation of the CS+ enhanced the unit response in the AC, PC, and DG, but it suppressed the firing of AV and MD neurons. Rare CS+ presentations did not alter AV and PC neuronal activity in Ss with subicular lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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

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

Acute inactivation of the inferior olive blocks associative learning

Can acute inactivation of the inferior olive block associative learning? We anaesthetized the inferior olive with lidocaine while rabbits simultaneously: (i) performed conditioned nictitating membrane responses to a flashing light to which they had already been trained; and (ii) underwent their first experience with classical conditioning of the same response to a tone. Inactivation of the inferior olive immediately and reversibly abolished the performance of conditioned responses and prevented learning during rabbits' initial conditioning with a tone-conditioned stimulus. When olivary function was restored, rabbits showed no signs of having learned under olivary anaesthesia. The experiment demonstrates that an acute disruption in olivary function can block learning, in addition to severely degrading motor control. The results are interpreted to indicate the importance of the inferior olive in optimizing learning, perhaps through a general role in regulating temporal processing.     

The Locus of Redundant-Targets and Nontargets Effects: Evidence From the Psychological Refractory Period Paradigm.

In target detection tasks, responses are faster when displays have 2 targets (redundant-targets effect; RTE) and slower when they have no targets (nontargets effect; NTE) relative to displays with a single target. The psychological refractory period paradigm was used to localize these effects. In Experiment 1, participants classified tones as high or low and then classified letters as targets or nontargets after a short or long stimulus onset asynchrony (SOA). The magnitudes of the RTE and NTE did not depend on SOA. In Experiment 2, the order of the tasks was reversed, and at short SOAs the RTE and NTE had similar magnitudes for both tone discrimination and target detection responses. These findings suggest that the RTE and NTE arise during response selection. Interactive effects of tone pitch with the number and type of target features were also observed, and these were tentatively interpreted as synesthetic effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of tone-dependent fear conditioning on heart rate and behavior of C57BL/6N mice.

The effects of the temporal sequence of tone (conditioned stimulus [CS]) and footshock (unconditioned stimulus [US]) during training (acquisition) on tone-dependent retention were studied in mice. Freezing increased significantly as an associative behavioral response in mice subjected to CS paired with US or after unpaired by 30 s in the memory test performed 24 hr after training. In the home cage of freely moving mice implanted with an electrocardiogram transmitter, CS triggered a strong tachycardiac response in the memory test. Heart rate (HR) increased from about 580 bpm to more than 750 bpm, and HR variability decreased significantly. The inhibition of the HR increase by the nonspecific β-adrenergic antagonist sotalol indicated the strong sympathetic contribution to the tachycardiac response. CS evoked a significant but minor HR increase in mice subjected to either CS or US only or CS and US unpaired by 60 s. Thus, HR and HR variability reflected associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Concomitant eyeblink and heart rate classical conditioning in young, middle-aged, and elderly human subjects.

Pavlovian heart rate (HR) and eyeblink (EB) conditioning were assessed in 4 groups of Ss who differed in age: young?=?19–33 yrs, young middle-aged?=?35–48 yrs, old middle-aged?=?50–63 yrs, and old?=?66–78 yrs. A 100-msec corneal airpuff was the unconditioned stimulus/stimuli (UCS) and a 600-msec tone was the CS. A nonassociative control group received explicitly unpaired tone and airpuff presentations. All Ss were studied for 2 100-trial sessions separated by approximately 7 days. An impairment in acquisition of both the EB and HR responses occurred in the old and middle-age Ss, but all age groups showed significantly greater conditioning than did the control group. Slight increases in performance resulted from a 2nd session of training. These findings suggest and age-related impairment in a general associative process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time course of cardiac conditioned responses in restrained rats as a function of the trace CS–US interval.

Two experiments aimed at understanding the temporal characteristics of trace-conditioned heart-rate responses to a 0.5-s tone (conditioned stimulus [CS]) in restrained rats. A CS paired with a tail-shock (unconditioned stimulus [UCS]) elicited lasting bradycardiac responses. The magnitude and extinction rate of conditioned responses (CR) were independent of the CS–US interval (interstimulus interval [ISI], 3 s to 20 s). Unreinforced test trials were analyzed for CR topography. Responding was delayed in groups with longer ISIs, but CR latencies, peak and decay times were not proportional to the ISI Response peaks tended to cluster either about 6 s after CS onset, or about 10 s with a slow decay, depending on the ISI. The authors postulated 2 components of auditory stimulus traces involved in cardiac conditioning, maximally active 6 s and 10 s respectively after CS onset. The topography of the CR could be constrained to combinations of associative strength and instantaneous activity of these 2 components. (PsycINFO Database Record (c) 2010 APA, all rights reserved)