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The effect of amygdalectomy on orienting and classical conditioning in monkeys.

The basic findings of these two studies are as follows: a failure of orientating and conditioning of viscero-autonomic responses, but essentially normal orienting and conditioning of a temporal muscle response in amygdalectomized animals. Small procedural differences exist between the two studies,and a possible order effect exists as a result of the use of the same subjects consecutively. However, we fell that the difference between the responses of the viscero-autonomic system and the skeletal system would still be found were all of the measures gathered simultaneously in an optimal conditioning situation. The definitive study--simultaneous viscero-autonomic and skeletal (behavioral) recording--remains to be done. Trial-by-trial analysis of the correlations or lack of correlations between these responses in such a study should be highly informative. These two studies offer substantial information relevant to the original questions. When behavior is modified by simple repetition of experience the effect of amygdalectomy is restricted to the viscero-autonomic components of orienting and classical conditioning, not to the entire spectrum of responses. The issue raised, therefore, is the significance of the viscero-autonomic components of orienting and classical conditioning. The suggestion has been proposed (Pribram, 1969) that these components serve as mechanisms of internal rehearsal necessary to the registration (as novel or familiar) of the orienting and conditioning experience. This proposal requires further testing.

Amygdala↗

Nefiracetam (DM-9384): effect on eyeblink classical conditioning in older rabbits.

The nootropic compound nefiracetam was evaluated in 88 older rabbits in a 750-ms delay paradigm of eyeblink classical conditioning (EBCC). Rabbits (mean age = 28.7 months) were assigned in groups of eight to one of six conditions in experiment 1: paired tone conditioned stimulus (CS)-corneal airpuff unconditioned stimulus (US) presentations and 1, 3, or 10 mg nefiracetam/kg or sterile saline vehicle; explicitly unpaired CS and US presentations and 3 mg nefiracetam/kg or sterile saline vehicle. Animals in the paired conditions received 10 daily sessions of 90 paired trials and animals in the unpaired conditions received 10 daily sessions of 180 unpaired CS and US presentations. The six conditions in experiment 2 were 5, 10, and 15 mg nefiracetam/kg and vehicle in 15 sessions of paired presentations; 10 mg nefiracetam/kg and vehicle in 15 sessions of unpaired conditioning. In both experiments 1 and 2, acquisition measured by trials to learning criterion was significantly faster at the 10 mg/kg dose of nefiracetam. In the repeated measures analyses comparing six doses in the paired conditions, all dependent measures [percentage conditioned responses (CRs), CR amplitude, and response latency] indicated significantly better conditioning in rabbits treated with 10 mg nefiracetam/kg, but this dose did not increase motor responding or responding in the unpaired condition. Nefiracetam facilitated acquisition of EBCC in older rabbits. EBCC is performed poorly by older humans and is seriously impaired in Alzheimer's disease. These preclinical data in an animal model with clear parallels in humans suggest that nefiracetam may prove effective as a cognition enhancer in clinical trials.

Acoustic Stimulation↗

A supratrigeminal region implicated in the classically conditioned nictitating membrane response.

The dorsolateral pontine brain stem was investigated as a possible locus of neural elements mediating the classically conditioned nictitating membrane (NM) response in rabbit. Recording and brain stimulation were employed for this purpose. Low-impedance tungsten monopolar microelectrodes were chronically implanted into the pontine brain stem. Multiple-unit recording during classical conditioning revealed a conditioned increase in multiple-unit activity (MUA) which developed and extinguished concurrently with the acquisition and extinction of the behavioral conditioned response. Pseudoconditioning and conditioned inhibition controls indicated that the increase in MUA was an associative learning phenomenon. Histology indicated that electrode tips recording the CR-associated electrical activity were located mostly adjacent or dorsal to the motor trigeminal nucleus. Periocular shock pulses elicited short latency evoked responses throughout most of the dorsolateral pons, suggesting that information concerning the unconditioned stimulus is relayed to this region. Furthermore, electrical stimulation of this region produced a robust ipsilateral nictitating membrane response in a number of cases, suggesting that neural elements of the dorsolateral pons project to the motoneurons that produce membrane extension. A consideration of several criteria based on these experiments implicates a supratrigeminal zone [22] as containing the neural elements of dorsolateral pons most intimately associated with the conditioned NM response. Other interpretations, concerning fibers of passage through this region and

Abducens Nerve↗

Classical conditioning, awareness, and brain systems.

Memory is composed of several different abilities that are supported by different brain systems. The distinction between declarative (conscious) and nondeclarative (non-conscious) memory has proved useful in understanding the nature of eyeblink classical conditioning - the best understood example of classical conditioning in vertebrates. In delay conditioning, the standard procedure, conditioning depends on the cerebellum and brainstem and is intact in amnesia. Trace conditioning, a variant of the standard procedure, depends additionally on the hippocampus and neocortex and is impaired in amnesia. Recent studies have sharpened the contrast between delay and trace conditioning by exploring the importance of awareness. We discuss these new findings in relation to the brain systems supporting eyeblink conditioning and suggest why awareness is important for trace conditioning but not for delay conditioning.

Journal Article↗

Haloperidol impairs classically conditioned nictitating membrane responses and conditioning-related cerebellar interpositus nucleus activity in rabbits.

Rabbits, chronically implanted with recording electrodes in the cerebellar interpositus nucleus and following acquisition of a classically conditioned eyelid response, were injected with haloperidol (HAL, 250 micrograms/kg). HAL significantly reduced the number of conditioned responses when a 75 and 85 dB tone conditioned stimulus (CS) was presented but not when a 95 dB tone CS was used. There was a corresponding decrease in interpositus activity at the 75 and 85 dB CS intensities but not at the 95 dB intensity. HAL appeared to disrupt CRs and interpositus activity by increasing the intensity threshold of the tone CS for eliciting conditioned responses. Possible mechanisms for the effect of HAL on neural circuitry involved in classical eyelid conditioning are discussed.

Animals↗

The effects of scopolamine, lorazepam, and glycopyrrolate on classical conditioning of the human eyeblink response.

Human eyeblink conditioning, a relatively simple form of learning and memory, has previously been shown to be impaired by the central and peripheral anticholinergic scopolamine. The present study compared the behavioral effects of scopolamine with the benzodiazepine lorazepam and a peripherally active anticholinergic, glycopyrrolate. Thirty-six healthy normal volunteers (mean age: 23.7 years) were studied with 12 assigned double-blind to each of three drug conditions (0.5 mg scopolamine IV, 2 mg lorazepam PO, or 0.2 mg glycopyrrolate IV). Subjects underwent classical conditioning of the eyeblink response in which the conditioned stimulus was an 80 dB binaural tone, and the unconditioned stimulus was a 2 psi airpuff to the right eye. Ten trials of unpaired stimulus presentations were followed by 60 paired trials and finally by an extinction period of five tone-alone presentations. An eyeblink response that occurred during the tone but before the airpuff was scored as a conditioned response (CR). Subjects treated with lorazepam (43% mean CRs) and scopolamine (51% mean CRs) exhibited a significantly lower asymptotic level of conditioning than those treated with glycopyrrolate (85% mean CRs; P < 0.01). However, during extinction, lorazepam-treated subjects (35% CRs) showed a lower overall level of responding to the tone than either scopolamine (60% CRs) or glycopyrrolate (62% CRs) treated subjects (P < 0.05). It seems unlikely that these differences could be accounted for by drug-induced alterations in motor responses because there were no significant differences between the three drug conditions in the frequency, latency, or amplitude of unconditioned responses to the airpuff. Overall, our data indicate that scopolamine and lorazepam impair eyeblink conditioning and suggest that some of the effects of benzodiazepines and anticholinergics on learning and memory can be differentiated using this paradigm.

Adult↗

Safety signals from avoidance learning but not from yoked classical conditioning training pass both summation and retardation tests for inhibition.

In one experiment half of the animals were trained to avoid a signaled footshock by jumping (30 or 160 trials), whereas the rest of the animals received the same events as yoked. For all of them the termination of the warning signal and of the shock was followed by a safety signal. Several tests were conducted to assess the ability of the stimuli to suppress licking by measuring the latency in completing 25 consecutive licks in the presence of the stimuli. Fear of the warning signal and inhibitory properties of the safety signal (summation and retardation tests) were measured. The results showed that there were no differences in fear to the warning signal, and that the safety signal behaves as a conditioned inhibitor only for animals trained with a long avoidance procedure, but not in the yoked (classical conditioning) procedure. These results highlight the role played by the avoidance response and its consequences in avoidance learning.

Animals↗

Fos-like immunoreactivity in locus coeruleus after classical conditioning of the rabbit's nictitating membrane response.

We investigated the changes in Fos-like immunoreactivity in the locus coeruleus (LC) after classical conditioning of the rabbit's nictitating membrane. Specifically, we compared unpaired versus paired presentations of a tone conditioned stimulus (CS) and a tactile unconditioned stimulus (US; near the eye). After two training sessions, only paired presentations resulted in acquisition of a conditioned response. This was associated with comparatively less LC Fos expression than with unpaired presentations. Similar observations have been reported for the ventrolateral medulla which is a major source of afferents to LC. The present results are consistent with a role of LC in attention and learning: activity increases as the animal attends to the CS and US. When the relationship between CS and US has been established, LC activity decreases.

Animals↗

Classical conditioning during human NREM sleep and response transfer to wakefulness.

To assess learning abilities during human NREM sleep stages, five subjects underwent simple classical conditioning during stages 2-4 using heart rate (HR) as a measure. Results show (a) significant conditioning effect was observed during slow wave sleep (SWS; stage 3 + 4) but not during stage 2; (b) some evidence was obtained to support the view that conditioning effect during sleep transferred to wakefulness.

Adult↗

Comparison of timing and classical conditioning.

Four experiments with rats investigated if the timing of a stimulus (sound) correlated with the strength of a conditioned response (CR) to the stimulus. The timing (effective duration) of the stimulus was measured using the peak procedure, similar to a discrete-trials fixed-interval procedure. The rats were trained so that their response rate reached a maximum about 40 s or 60 s after the onset of a light; the time of the maximum measured from the start of the light (peak time) was the measure of timing. On some trials, the light was preceded by a short (5 s) or long (20 s or 30 s) interval of sound. We assumed that the difference in peak time after long and short sounds reflected the timing of the sound--if the sound was timed, the longer sound would produce a lower peak time; if the sound was not timed, the two durations of sound would produce the same peak time. The CR was lever-pressing during the sound. The sound was treated in various ways: presented alone (Experiments 1, 3, and 4), followed by food (Experiments 1, 3, and 4), preceded by food (Experiment 3), and followed by food after 20 s (Experiment 4). Treatments that produced no timing of sound produced no CR, and treatments that increased (or diseased) timing also increased (or decreased) the CR. The results suggest that there is overlap between the mechanisms that produce time discrimination and the mechanisms that produce classical conditioning.

Animals↗

Activity of deep cerebellar nuclear cells during classical conditioning of nictitating membrane extension in rabbits.

The activity of neurons in the interposed and dentate nuclei of the cerebellum was investigated during differential classical conditioning of the rabbit eye blink nictitating membrane response. Forty-seven percent of the 165 cells in the study responded to the orbital stimulation used as the unconditioned stimulus (US). The latency distribution of US-elicited responses was bimodal with peaks at 7 and 19 ms. Twenty-one percent of the cells responded with short latencies to the tones used as conditioned stimuli (CSs). These cells typically responded to both the reinforced and nonreinforced CSs. Forty-one percent of the cells responded on conditioned response (CR) trials but not on trials without CRs. The average lead of the neural response to the CR was 71.4 ms. Cells that responded on CR trials were more likely to respond to the CSs, or to the CSs and the US, than cells that did not respond on CR trials. For about half of the cells that responded on CR trials the latency of response followed trial-by-trial variations of CR latency. For the remainder, the response was time-locked to CS-onset. Cells whose responses paralleled the CR may be involved in the initiation or modulation of the CR, while those whose responses were time-locked to the CS may be involved in sensory processing underlying the initiation of the movement. The pathways that may underlie the US- and CS-elicited responses are also discussed.

Animals↗

Rabbit classically conditioned eyelid responses do not reappear after interpositus nucleus lesion and extensive post-lesion training.

The left eyelid responses of four rabbits were classical conditioned by pairing a tone conditioned stimulus and air puff unconditioned stimulus. After conditioned responses were well-established, the left interpositus nucleus was lesioned and 150-200 post-lesion training sessions, distributed over 10 months, were given. In three of the rabbits, no anticipatory conditioned responses were observed on paired trials and responses were at or below spontaneous blinking rates on 2,500 ms CS-alone trials that were also presented. Post-lesion conditioned responses were present when the right side was trained. The fourth rabbit showed few post-lesion conditioned responses on paired trials but eventually showed 80% conditioned responses on tone-alone trials. Histological analysis of the lesion extents indicate that a portion of the anterior interpositus nucleus was spared in this rabbit. These results argue that unlike other cerebellar lesion effects reported in the literature, where some recovery of function is normally noted, the effects of interpositus nucleus lesions are somewhat unique in that conditioned response abolition is seen as long as 10 months after the lesion.

Animals↗

Suppression of vasopressin secretion by classically conditioned stimuli in rats.

The possibility that emotional stress suppresses footshock-induced secretion of antidiuretic hormone (VP) was tested in rats by a classical conditioning paradigm. As a training trial, rats received a flash and a brief sound (2 kHz, 0.5 s) as conditioned stimuli (CS) followed by footshocks (FS, 5 ms pulses of 3 mA intensity, 50 Hz) for 1 s period as unconditioned stimuli. Rats were trained by 100 trials repeated at an interval of 6 s. A various length of time after the training, rats were tested by CS repeated at an interval of 15 s for the period of 120 s and FS of 60 s period, which started 60 s after the CS onset. Testing CS further augmented FS-induced increase in plasma adrenocorticotrophic hormone (ACTH) but suppressed FS-induced increase in plasma VP in a time-dependent manner. The CS also increased the degree of an inhibition of motor behavior known as "freezing" behavior. Augmentation of ACTH response and suppression of VP response to testing FS were dependent on the training shock intensity. These data are consistent with the hypothesis that VP secretion is potentiated by physical but suppressed by emotional stress.

Animals↗

Information variables in voluntary control and classical conditioning of heart rate: field dependence and heart-rate perception.

Two experiments focused on two information variables relevant to changes in heart rate, field dependence and the ability to perceive one's own heart rate. In Exp. I, 14 field-independent and 17 field-dependent subjects completed a heart-rate perception and a voluntary heart-rate control task. The anticipated superiority in heart-rate control by field-independent subjects was detected although no evidence was found for a relationship between the amount of biofeedback available in the situation and voluntary control of the cardiovascular system. Exp. II involved 9 field-independent and 8 field-dependent subjects in a classical conditioning paradigm involving shock sensitivity. In contrast with Exp. I, in this phase of the study heart-rate increases were correlated with the ability of the subject to discriminate heart beats, especially for the field-independent group. It was concluded that field dependence and heart-rate perception are related to classically conditioned heart-rate increase for some subjects and further that field dependence may be a potent variable operating in those situations involving the voluntary control of heart rate without exteroceptive feedback.

Biofeedback, Psychology↗

Nonaware classical conditioning to pictorial facial stimuli in a between-groups paradigm.

The present experiment investigated the effects of aware and nonaware modes of extinction in classical conditioning to facial emotional stimuli. The subjects participated in three different experimental phases. In the first (habituation) phase they were presented with a 500 ms angry face. In the second (acquisition) phase, for half of the subjects the 500 ms face was paired with an aversive noise (experimental group) while for the other half of the subjects the face and the noise presentations were separated by 6-10 s intervals (sensitization control group). In the third (extinction) phase, these two groups were further divided into two subgroups. One subgroup of both the experimental and control group had the face stimulus presented for 30 ms, and immediately masked with a neutral picture. The other two subgroups had the face presented for 500 ms with no mask. The results showed that conditioning only occurred in the experimental subgroups which was indicated by a significant difference between skin conductance responses during habituation and corresponding responses during extinction. Secondly, comparing the experimental and control groups during the extinction phase, a significant conditioning effect was observed for both the aware and nonaware masked modes of extinction for the experimental group. The results suggest that conditioned autonomic responses may be elicited in a nonaware mode.

Adolescent↗

The continuing problem of post chemotherapy nausea and vomiting: contributions of classical conditioning.

Despite continuing improvements in antiemetic therapies, nausea and vomiting following chemotherapy treatments for cancer remain significant clinical problems for many patients. The role of classical conditioning in patients' anticipatory nausea is well known, but little attention has been paid to possible conditioning effects on post treatment nausea. The present study statistically examined the contribution of anticipatory (conditioned) nausea to patients' subsequent post treatment nausea. Forty early stage breast cancer patients who developed anticipatory nausea were analyzed. Results revealed a significant correlation between the intensity of anticipatory nausea in the clinic prior to their treatment infusion and subsequent post treatment nausea during the 24 h after the infusion. These results provide support for the hypothesis that, once established, conditioned nausea may contribute to the severity of subsequent post treatment nausea in patients receiving repeated cycles of chemotherapy for cancer. The results suggest the importance of considering the contribution of conditioning process to nausea and other post treatment side effects.

Antineoplastic Combined Chemotherapy Protocols↗

Opiates and classical conditioning: selective abolition of conditioned responses by activation of opiate receptors within the central nervous system.

It has previously been shown that opiates produce selective abolition of aversively motivated classically conditioned responses in the rabbit. The experiments reported here show that these effects are mediated by specific activation of opiate receptors within the central nervous system in that this central activation is both necessary and sufficient to produce opiate-induced abolition of conditioned responding. Further characterization suggests that selective activation through opiate-mu-receptor interactions within the periaqueductal gray/periventricular region of the fourth ventricle may be critical in mediating this abolition.

Avoidance Learning↗

Classical conditioning of decreases in human systolic blood pressure.

Decrease in human systolic blood pressure of 4.35 mm Hg (range: 0 to 12 mm Hg) were classically conditioned in normal and hypertensive subjects using a delayed conditioning paradigm in which a 30-sec auditory stimulus (the conditioned stimulus) was followed immediately by tilting the subject 15degrees head-down to elicit small decreases in blood pressure. Conditioning occurred within five trials. A control group demonstrated that sensitization of the reflex by repeated tilting could not account for the blood-pressure decreases associated with the conditioned stimulus in experimental subjects.

Acoustic Stimulation↗