Classical conditioning is most effective when a us that is paired with a cs are:

Respondent or Pavlovian Conditioning

Gentry and Bernal (1977) were the first to describe a respondent model of the development of chronic pain. They suggested that acute pain (the US) associated with sympathetic activation and increased generalized muscle tension (the UR) may evolve into a chronic pain problem through a process of classic conditioning. In their model, the frequent association of innocuous stimuli (CSs), such as a certain environment or a certain body position with acute pain states, may elicit fear of pain, sympathetic activation, and increased muscle tension (the CR) in response to these previously neutral stimuli. Gentry and Bernal further suggested that this process of conditioning might lead to a pain–tension cycle that could maintain the chronic pain problem independent of the original tissue damage. Thus, the pain resulting from this process may be a purely musculoskeletal type of pain completely unrelated to the original cause of the pain.

Linton and co-authors (1985) further elaborated on the respondent conditioning perspective of chronic pain and emphasized that there is a wide range of stimuli that may serve as CSs and USs. They pointed out that both direct and indirect noxious stimuli (e.g., pain originating from a herniated disc, carrying something heavy with a problem back) may be important USs. Whereas the US may be related to an injury, the UR is usually manifested as activation of the sympathetic nervous system, anxiety, and increases in muscle tension. The CS related to the US and the CR is not pain initially but can be pain provoking over time.Linton and colleagues (1985) stated that there is no evidence of classic conditioning of pain per se, only of anxiety and related physiological activation. This elevated anxiety may then lead to heightened sensitivity to noxious stimuli (Vlaeyen and Linton 2000). Whether the muscle tension produced by muscle contraction leads to pain is dependent on the amount of muscle contraction, its duration, and individual vulnerability (predispositional factors such as previous injury or genetic variables). The pain produced by muscle tension may thus not be the same as the original pain; however, patients (and physicians) may not be able to discriminate between the two.

Preliminary evidence supports the role of respondent conditioning in chronic pain patients. For example, patients who have upper back pain and healthy controls received USs (painful electric stimulation) to the forearm; a picture of a dead body (thought to have high belongingness with pain) served as a positive CS (followed by shock most of the time), and a picture of a rabbit (positive cue unrelated to pain) served as a negative CS (never followed by shock). The chronic back pain patients showed anticipatory high muscle tension in the arm in the preconditioning phase when the dead body was never followed by pain. In the learning phase they showed an increase in the muscular response in the arm close to where the painful stimulus was applied and, in addition, displayed CRs in the trapezius muscle (Schneider et al 2004; see alsoVlaeyen et al 1999).

Abstract

Classical conditioning was first discovered by Ivan P. Pavlov in the early 1900s. It can be conceptualized as learning about event sequences that occur independently of one's actions in one's environment. Specifically, one learns that a preceding event (stimulus) becomes a signal for a subsequent event. This article touches on a variety of issues. It provides examples of classical conditioning with humans, describes different forms of classical conditioning, elaborates on one of many models of classical conditioning, presents a few of the key phenomena, and finally illustrates application of classical conditioning to some treatments of clinical conditions such as phobias and drug addiction.

Learning and Memory

Anterograde amnesia, one of the core desirable anesthetic end points, is achieved at lower anesthetic concentrations (∼0.25 MAC) than those required for unconsciousness (∼0.5 MAC). Perhaps the closest analogue in rodents to explicit memory in humans is medial temporal lobe–dependentlearning of temporal and spatial sequences known ashippocampus-dependent spatial learning. Other learning paradigms, such as fear conditioning to tone, are by contrast independent of the hippocampus. Spatial learning can be tested by a variety of experimental paradigms, including fear conditioning to context (Fig. 19.5). Isoflurane and the nonimmobilizer F6 both inhibit hippocampus-dependent learning at about half the concentration necessary for disrupting hippocampus-independent learning.84 Similarly, anesthetic concentrations that inhibit explicit memory in humans (memory that can be explicitly recalled as opposed to motor learning, classical conditioning, and so on) are similarly lower than concentrations that impair implicit memory (not subject to willful recollection).85 Taken together, these findings implicate effects on function of the medial temporal lobe, including the hippocampus, in the suppression of explicit memory by anesthetics. Effects on other structures, such as the amygdala, may be relevant to anesthetic impairment of implicit or other types of memory.86

Because inhaled anesthetics affect multiple cellular targets even at amnesic concentrations, it is likely that anesthetic-induced amnesia arises from multiple cellular-level changes. A quantitative comparison of the degree of change in synaptic inhibition in the hippocampus produced by equiamnestic concentrations of isoflurane versus etomidate indicated that the enhancement of GABAergic inhibition can account for a substantial portion of isoflurane’s effect on memory.87 Other contributing targets may include nAChRs,88 HCN1 channels,89 and excitatory glutamatergic synapses,90 Conversely, it is also likely that suppression of learning and memory by drugs known to have different receptor affinities share common mechanisms at some level of integration. For example, θ-rhythms (4-12 Hz) are clearly important for hippocampus-dependent learning and memory.91 Benzodiazepines92 and cannabinoids93 slow and suppress hippocampal θ-rhythms in proportion to their ability to impair hippocampus-dependent learning. Isoflurane and the nonimmobilizer F6 have comparable effects on θ-rhythms at amnesic concentrations while having different receptor-level profiles and opposite effects on sedation.94 Thus alterations in neuronal synchrony mayprovide a common network-level substrate for memory impairment. The synchronization between amygdalar and hippocampal θ-rhythms that occurs during fear memory retrieval indicates that this principle might also apply to other forms of memory and their impairment by anesthetics.95 As with other components of the anesthetic state, the precise mechanisms of memory impairment by anesthetics and of memory itself remain to be fully elucidated.

V.B.1.b.iv. Fear Classical Conditioning

Classical conditioning has been increasingly used to study the learning of fear. This paradigm can be considered a hybrid of autonomic and somatic classical conditioning because fear causes numerous autonomic changes, which could be measured as the CR. However, in the rat, the most common subject for studies of this type, fear can also be measured with the somatic response of freezing. In the typical paradigm, a tone CS is paired with a shock US. The shock US is delivered to the rat through an electrified floor grid. With pairing of the CS and the US, a fear CR develops in response to the CS. In this case, the fear CR is freezing (the rat holds completely still).

Physiologic Conditioning

Early conditioning experiences may also influence physiologic functioning and the development of psychophysiologic disorders. Psychophysiologic reactions involve psychologically induced alterations in the function of target organs, without structural change. They are often viewed as physiologic concomitants of emotions such as anger or fear, although the person is not always aware of these emotions. Persistence of an altered physiologic state or an enhanced physiologic response to psychological stimuli is considered a psychophysiologic disorder by some researchers. Visceral functions such as secretion of digestive juices and motility of the gallbladder, stomach, and intestine can be classically conditioned24 even by family interaction.Classical conditioning, as described by Pavlov, involves linking an unconditioned stimulus (sound of a bell) with a conditioned stimulus (food) that elicits a conditioned response (salivation). After several trials, the unconditioned stimulus can produce the conditioned response. It has been demonstrated that fear of benign GI sensations can be acquired through classical conditioning, a finding that has implications for newer behavioral treatments that incorporate exposure-based techniques (see later).25 In the first study of its kind, 52 healthy participants with no history of GI symptoms were randomized to either a condition in which a nonpainful esophageal balloon distention preceded a painful one (experimental) or to a condition in which the painful condition was administered butnot paired with the benign balloon distension (control). The experimental group demonstrated higher pain expectancy, augmented skin conductance response, and a potentiated startle reflex in response to benign balloon distention but fortunately were able to be deconditioned through an extinction paradigm after the experiment was completed.26

By contrast,operant conditioning involves development of a desired response through motivation and reinforcement. Playing basketball is an example; accuracy improves through practice, andthe correct behavior is reinforced by the reward of scoring a basket. Consider the following case:

In this case, the parent focused on the abdominal discomfort as an illness that required absence from school rather than as a physiologic response to a distressing situation. Staying home allowed the child to avoid the feared situation without addressing the determinants of the fear. Repetition of the feared situation may then lead to a conditionally enhanced psychophysiologic symptom response and may also alter the child’s perception of these symptoms as an illness, leading to health care–seeking behaviors later in life (illness modeling).27 Children whose mothers reinforce illness behavior have been found to experience more severe stomach aches and more school absences than other children.23

VI. Summary

Classical conditioning theories have become considerably more complex since the early formulations by O. H. Mowrer and others. Modern conditioning models emphasize the role of cognitive factors such as memory processes and expectancies in the etiology and maintenance of conditioned responses. As theories of fear have developed, other pathways to fear acquisition have been added, although classical conditioning continues to be seen as important. Classical conditioning theories have led to a number of important treatments, with the most widely used being the exposure therapies for reducing fear. According to contemporary views, extinction of the CR can be regarded as a process of exposure to corrective information. Exposure involves having the person repeatedly exposure himself or herself to a feared stimulus until fear abates. Patients play an active role in choosing what they will be exposed to, and when the exposure will occur. Exposure therapies can successfully reduce conditioned fears and fears arising from other forms of learning.

Of the exposure therapies, graded in vivo exposure and flooding are among the most effective treatments of phobias, and play an important role in treating disorders in which fear plays a prominent role (e.g., social phobia, agoraphobia). For patients who are extremely phobic, the least demanding form of exposure (systematic de-sensitization) is typically the exposure intervention to be used first. Graded in vivo exposure is particularly important because it involves teaching patients skills for overcoming their fears. Patients can continue to apply these skills on their own, without the aid of a therapist. Exposure therapies can be combined with other psychological interventions, such as relaxation training and cognitive restructuring. For the average phobic patient, combination treatments tend to be no more effective than exposure alone. However, there are likely to be exceptions to this rule, and some patients may benefit most from a combination of psychotherapeutic procedures. Combining exposure with antianxiety drugs does not improve outcome, and may actually impair the effects of exposure. The benefits of exposure therapy tend to be long lasting, with no evidence of symptom substitution. Patients sometimes relapse, although their reemergent fears can usually be successfully treated with a further course of exposure therapy.

2 Basic Conditioning Procedure

The procedure of classical conditioning consists of the repeated presentation of two stimuli in temporal contiguity. First, a neutral stimulus (NS) is presented—that is, a stimulus that does not elicit regular responses or responses similar to the unconditioned response (UR). Immediately after that, the US is presented. Because of this pairing, the NS will become a CS and, therefore, will be capable of provoking a conditioned response (CR) similar to the UR that, initially, only the US could elicit (Fig. 1).

On the initial trials, only the US will elicit the salivation response. However, as the conditioning trials continue, the dog will begin to salivate as soon as the CS is presented. In salivary conditioning, the CR and the UR are both salivation. However, in many other conditioning situations, the CR is very different from the UR. According to Pavlov, the animals learn the connection between stimulus and response (CS–UR). Currently, it is understood that animals learn the connection between stimuli.

Publisher Summary

This chapter provides an overview of classical conditioning concept in learning behavior. While classical conditioning is often thought of as a simpler form of learning than operant conditioning; in fact, the complexity of classical conditioning from a procedural viewpoint rivals that of operant conditioning. It is generally agreed that classical conditioning, along with operant conditioning, constitutes the majority, if not all, of the learned behaviors. In general, classical conditioning involves the pairing of two stimulus events, typically a neutral conditioned stimulus (CS), and an unconditioned stimulus (US). That an association between these two events is learned is reflected in the acquisition of a conditioned response (CR) to the CS. The CR is usually topographically similar in the form to the unconditioned response (UR) to the US, although this is not universally the case. However, for classical conditioning the CR in no way changes the CS–US stimulus arrangements. One area where classical conditioning has been used extensively is in the study of drug effects on learning or acquisition. Classical conditioning procedures hold a number of advantages over operant conditioning in the study of learning.

Classical Conditioning of the Eyeblink Response

Whereas Ivan Pavlov discovered the phenomenon of classical conditioning using a conditioned reflex in the autonomic nervous system, the conditioned reflexes used in contemporary studies of classical conditioning, such as the conditioned eyeblink response, are controlled in the central nervous system. Skeletal muscle innervated by the cranial nerves controls the eyeblink. Eyeblink classical conditioning is a common paradigm for investigations of classical conditioning in general and classical conditioning in normal aging in particular. Fear conditioning, in which a neutral CS is paired with a moderately painful US, is another promising model system that has been elaborated extensively on a behavioral and neurobiological level. Studies of aging effects on fear conditioning have been reported, but the results are not consistent. The magnitude of age-related fear responses appears to be small, especially in comparison with age-related changes in eyeblink classical conditioning.

The neural circuitry that supports classical conditioning of the eyeblink response is almost completely mapped, and the behavioral and neurobiological parallels in this form of associative learning extend to all mammals that have been studied, including humans. Processes of normal aging affect eyeblink classical conditioning similarly in all species in which older organisms have been tested – mice, rats, rabbits, cats, and humans.

For several decades, the promise of eyeblink classical conditioning as a model system for the study of learning and memory in aging has been evident. Among the significant advantages of this model system for investigating processes of normal aging are that (1) age differences in the classically conditioned eyeblink responses are large and (2) striking parallels exist between the age differences in eyeblink conditioning in nonhuman mammals and humans. The initial parallels in normal aging and eyeblink conditioning were demonstrated between rabbits and humans. On no other species is there such a large body of parametric data on classical conditioning as on the classically conditioned eyeblink response in the rabbit. Indeed, much of the general literature on classical conditioning is based on data collected in the rabbit with the nictitating membrane (third eyelid of the rabbit) response and in the human with the eyeblink. Now techniques for behavioral and electrophysiological testing in rats, including neonatal rats, have been developed, along with techniques to test eyeblink conditioning in normal, mutant, and transgenic mice and rodent slice preparations.

Ernest Hilgard was the first to study eyeblink classical conditioning in animals and did classic studies on human eyeblink conditioning as well. His work established the close correspondence in properties of the conditioned eyeblink response in humans and others animals, suggesting that the underlying neuronal mechanisms of memory storage and retrieval are the same in all mammals, including humans. Here, perhaps more than in any other form of learning, neuronal mechanisms of memory elucidated in infrahuman mammals apply directly to the human condition. Isadore Gormezano was the first to publish eyeblink conditioning studies in the rabbit and to introduce measurement of the nictitating membrane extension response.

Initial research on aging and classical conditioning studied rabbits or humans. However, there are advantages of other species, such as mice and rats, for research on aging. In particular, mice and rats, with their short gestation period, large litter size, relatively small space requirements, and short life spans, are highly desirable for research on development and aging. Neither the genetic controls nor the breeding environments presently available for rabbits equal those in place for the mouse and rat. Consequently, many of the recently published studies on eyeblink classical conditioning, including those on aging, involve rodent subjects.

B. The Rabbit Model System of Nictitating Membrane/Eyeblink Classical Conditioning

Much of the general literature on classical conditioning is based on data collected with the human eyeblink conditioning paradigm and in the rabbit nictitating membrane or “third eyelid” paradigm first introduced by Isadore Gormezano (Gormezano et al., 1962; Schneiderman et al., 1962). Evidence has converged from a number of sources to suggest that the cerebellum ipsilateral to the conditioned eye is essential for eyeblink classical conditioning in rabbits and humans.

The most extensive body of literature linking the cerebellum and eyeblink classical conditioning comes from research with animals. This research is eloquently described by its primary instigator and motivator, Richard F. Thompson et al., this volume, and will be mentioned only briefly here. A variety of techniques including electrophysiological recording of multiple and single units, electrolytic and chemical lesions, physical and chemical reversible lesions, neural stimulation, genetic mutations, and pharmacological manipulation have been used to demonstrate that the dorsolateral interpositus nucleus ipsilateral to the conditioned eye is the essential site for acquisition and retention (Berthier and Moore, 1986, 1990; Chen et al., 1996; Clark et al., 1992; Gould and Steinmetz, 1994; Krupa et al., 1993; Lavond et al., 1985; Lincoln et al., 1982; McCormick et al., 1981; McCormick and Thompson, 1984a,b; Steinmetz et al., 1992; Thompson, 1986, 1990; Yeo et al., 1985). Involvement of the cerebellar cortex has also been demonstrated during normal acquisition, although it may not be essential (Chen et al., 1996; Lavond and Steinmetz, 1989).