Habituation Research Paper

With these words, Sharpless and Jasper introduced their now classic study of habituation of the electroencephalogram (EEG) arousal response. Their study had a profound impact on behavioral neuroscience avnd served to kindle the interest of neural scientists in brain mechanisms of habituation. Habituation is a decrease in response to repeated stimulation, and sensitization is an increase in response as a result of stimulation. Virtually all behavioral responses, as well as autonomic and EEG responses and signs of arousal, habituate rapidly and to a profound degree. The processes responsible for habituation of behavioral responses probably occur largely after the primary sensory pathways of the brain and before the motor neurons that move muscles—somewhere between initial processing of sensory information and the execution of decisions to respond. Sensitization, the increase in response that often occurs when strong stimuli are given, may be similarly localized, although some evidence indicates that sensitization may occur in motor systems and motor neurons.

In early work on brain processes of habituation, it was thought that virtually all measures of neural activity might habituate, ranging from first-order sensory nuclei to the cerebral cortex. An early experiment to report evoked response habituation was that of Hernandez-Peon et al. (1957); they recorded responses to click stimulation at several levels of the auditory system. Trains of clicks were delivered once every two seconds for long periods of time and evoked responses of the cochlear nucleus (the first relay of the auditory system) were reported to habituate.

Careful studies by Worden and associates (see Marsh et al. 1962) demonstrated that click-evoked responses at the cochlear nucleus do not show habituation. Instead, amplitudes of responses at this first relay nucleus in the auditory system are rigidly controlled by the physical properties of the sound stimulus. Because of acoustic factors, the intensity of a sound is often weaker at the floor of a test cage. If an animal gradually became bored and rested his head on the floor, the cochlear nucleus-evoked response to click would decrease because of reduced sound intensity.

In an extensive and careful study, Wickelgren (1968) found that habituation of evoked responses to auditory stimuli was not prominent below the level of the thalamus and cortex in the auditory system. This appears to be a general finding in all sensory systems—the lower ascending relay nuclei do not exhibit habituation. It would be most surprising if there were marked habituation in sensory systems. If our sensory systems habituated to sensory stimuli, we would rapidly cease to have sensation—a most unadaptive state of affairs. However, behavioral responses and phenomena that seem to be related to the probability of behavioral responding, such as EEG arousal and autonomic signs of orienting, show marked habituation. It is very adaptive to cease responding to arousing stimuli that have no particular significance.

Historically, such processes as habituation and sensitization were viewed simply as reflexes and not as phenomena of learning and memory. However, the broad definition of learning as a change in behavior as a result of experience certainly encompasses both phenomena. When this was recognized, analysis of neural mechanisms became ‘legitimized’ (Sharpless and Jasper 1956, Thompson and Spencer 1966). Habituation and sensitization are now seen as examples of nonassociative learning and memory. Greater progress has been made in analysis of the basic neuronal mechanisms underlying habituation than in more complex forms of behavioral plasticity such as classical and instrumental conditioning. Major reasons for this progress lie in the widespread occurrence of habituation, in its simplicity, and in the reliability with which the behavioral properties of habituation can be specified and determined. Habituation occurs both in spinal reflexes of the vertebrate (Sherrington 1906) and for responses of simple animals, as well as in complex human behavior. Consequently, neural mechanisms of habituation can be studies in simplified systems.

As noted earlier, behavioral habituation is simply response decrement as a result of repeated stimulation. For example, if a moderate electric shock is delivered to the foot of a normal but restrained animal for the first time, the animal will show marked struggling and leg flexion movements. However, if the stimulus is repeated a few times, the responses decrease considerably and may even disappear. Habituation is commonly differentiated from response decrements due to trauma, growth, aging, etc. In the example above, if the shock to the foot is withheld for a period of time after habituation and then given again, the response will reappear with normal strength. This spontaneous recovery is a common control used to show that habituation is a reversible response decrement.

Response decrements due to altered sensitivity of receptors are often termed receptor adaptation, and response decrements due to decremental effects occurring at the neuromuscular junctions of muscles are often termed muscular fatigue. Neither of these processes is considered to be habituation; it is a central rather than a peripheral process. Almost all behavioral responses of the intact organism initially elicited by a given stimulus, ranging in complexity from leg flexion to exploratory and play behavior, show habituation with repeated stimulation.

Response sensitization may be defined simply as an increased response strength to a given stimulus as a result of some other, usually strong, stimulus. The galvanic skin reflex (GSR) is a good case in point. Suppose we were to measure the GSR activity of sweat glands in the palm of the hand in response to a sound of moderate intensity. The response would probably be of relatively low amplitude and somewhat irregular in occurrence. If a strong shock were delivered to the skin, the sound alone now would evoke a much larger GSR response; the response would have been sensitized. The response increase due to sensitization is distinguished from conditioning in that no pairing of shock and sound is necessary to produce the effect. Sensitization itself typically habituates; after a number of shock presentations the response to the sound decreases to the initial weak level. In fact, it seems to decay spontaneously following a sensitizing stimulus.

The study of habituation has a long history; some of its basic properties were described in classic works by Jennings (1906), Humphrey (1933), Prosser and Hunter (1936), and Harris (1943). Thompson and Spencer (1966) surveyed the by then very extensive behavioral literature on habituation and identified some nine basic parametric properties or characteristics exhibited by behavioral habituation.

1. Properties Of Habituation

(a) Given that a particular stimulus elicits a response, repeated applications of the stimulus result in decreased response (habituation). The decrease is usually a negative exponential function of the number of stimulus presentations.

 (b) If the stimulus is withheld, the response tends to recover over time (spontaneous recovery).

(c) If repeated series of habituation training and spontaneous recovery are given, habituation becomes successively more rapid (this might be called potentiation of habituation).

(d) Other things being equal, the more rapid the frequency of stimulation, the more rapid and/or more pronounced is habituation.

(e) The weaker the stimulus, the more rapid and/or more pronounced is habituation. Strong stimuli may yield no significant habituation.

(f ) The effects of habituation training may proceed beyond zero or asymptotic response level.

(g) Habituation of response to a given stimulus exhibits stimulus generalization to other stimuli.

(h) Presentation of another (usually strong) sensitizing stimulus results in recovery of the habituated response (dishabituation or sensitization).

(i) Upon repeated application of the sensitizing stimulus, the amount of dishabituation produced habituates (this might be called habituation of sensitization).

It is important to emphasize that these characteristics of habituation are simply the empirically observed properties in a wide variety of behavioral studies on many species and as such do not imply particular theories or inferences. These properties have come to serve as the detailed definition of habituation. Thus, any particular stimulus-response system is said to exhibit habituation if the response decrement to repeated stimulation exhibits these properties.

The most potent variables determining the course of habituation are stimulus frequency and intensity. The frequency range must be behaviorally relevant. Very high frequencies can yield fatigue, potentiation, and other processes. The range of stimulus frequencies over which habituation occurs, i.e., behavioral response decrements exhibiting the properties noted above, is an empirical question dependent upon the organism, the stimulus, and the response system engaged. For the orienting or arousal response, the effective range may be from minutes to hours to days; for the spinal flexion reflex, the range is over seconds. The fact that rate and degree of habituation are inversely related to stimulus intensity (property (e)) is true if the same intensity is used for test and habituating stimuli (the test stimulus is given sufficiently infrequently that it does not by itself cause habituation). However, if the test and habituating stimuli differ in intensity, more complex effects can occur (Davis and Wagner 1968).

2. Dishabituation vs. Sensitization

Thompson and Spencer (1966) employed habituation of the spinal flexion reflex, first used as a model system to study habituation by Prosser and Hunter (1936), to characterize the detailed properties of habituation and analyze possible neuronal mechanisms. They discovered that the process of ‘dishabituation’ caused by presentation of a strong extra stimuli was not in fact dishabituation. That is, it did not disrupt the process of habituation at all. Instead, it added a superimposed, independent process of increased excitability, namely sensitization. The fact that dishabituation, per se, does not appear to exist as such, but rather reflects a separate process of sensitization, appears to hold for all vertebrate preparations studied, ranging from reflexes to the startle response to EEG arousal and the orienting response. One exception to this rule has been reported for a monosynaptic system in the invertebrate Aplysia (Marcus et al. 1988). However, the neuronal mechanisms underlying the processes of sensitization dishabituation appear to differ in vertebrates vs. the Aplysia circuit. In the latter, ‘dishabituation’ appears to be a presynaptic process, occurring at the sensory neuron terminals on the motor neurons (see Sect. 3 and Kandel 1976); whereas, at least in spinal reflexes, sensitization can involve increased excitability in motor neurons (Thompson and Spencer 1966). Actually, recent evidence suggests that changes may occur in motor neurons in the Aplysia circuit as well (Murphy and Glanzman 1997).

The fact that dishabituation does not exist as such, but rather reflects a separate independent process of sensitization in vertebrate preparations led Groves and Thompson (1970) to develop the dual-process theory of habituation: the outcome of repeated stimulus presentations is due to the net interaction of the inferred processes of habituation and sensitization. This theory is able to account for an astonishingly wide range of behavioral phenomena (see, e.g., Peeke and Herz 1973).

A somewhat differently construed and widely influential theory of habituation is the stimulus-model comparator theory developed in Russia by Evgeny Sokolov (1963), based largely on data from the human orienting response. In this view, repetition of a given stimulus results in the development of a neuronal ‘model’ of the stimulus in forebrain structures. If a repetitive stimulus matches the model, then there is little output, only the habituated response, which could be no response, i.e., no EEG arousal. However, if there is a mismatch, then the difference is amplified via the reticular formation and a larger response results.

The dual-process theory is more successful in accounting for basic phenomena of habituation and sensitization in a wide range of species; the modelcomparator theory can more easily account for more complex phenomena like the ‘missing stimulus’ effect (increased response to the absence of one presentation of the habituating stimulus, a phenomenon sometimes seen in EEG arousal but not in reflex systems). But note that a process of synaptic depression could underlie the formation of the neuronal model of the stimulus in the model-comparator theory; the theories are at different levels and not incompatible. A view somewhat similar to that of Sokolov was developed by Wagner (1979) to account for long-term habituation. Thus, the central model of the habituating stimulus is considered as a relatively long-term memory trace, yielding the basic properties of a learned response. In their classic study of human EEG arousal habituation, Sharpless and Jasper (1956) stressed the distinction between short-term and long-term habituation.

As noted earlier, primary sensory afferent system neurons do not exhibit habituation. This makes perfect sense; in order to ‘decide’ how much to respond to a stimulus it is necessary to know what the stimulus is. Virtually all behavioral responses elicited by stimuli show habituation to repeated stimulation under at least some conditions. Central brain processes that are behavior-related like cortical EEG arousal show clear habituation, as do brain motor systems. Davis and associates completed a comprehensive analysis of the startle circuit and startle habituation in the rat (Davis 1984). The circuit includes auditory relay nuclei: the cochlear nuclei and the nuclei of the lateral lemiscus; a nucleus in the brainstem reticular system (nucleus reticularis pontis caudalis) and its projections to brainstem and spinal cord premotor and motor nuclei. Evidence suggests that habituation to the acoustic startle stimulus occurred before the motor systems, i.e., at the nucleus reticularis pontis caudalis (Davis et al. 1982). The reticular nucleus is a ‘bridge’ nucleus between sensory and motor systems.

3. Neural Mechanisms

Unlike associative learning, in habituation the stimulus-response neuronal circuit is hardwired. In systems where some degree of analysis of neuronal mechanisms is possible, the neural substrate of habituation occurs within the stimulus-response circuit itself and is not due to any extrinsic circuit action like external inhibition acting on the habituating circuit.

Greatest progress in analyzing neural mechanisms of habituation and sensitization has come from simplified neuronal systems. Two of these are the gill withdrawal reflex of the mollusk Aplysia and vertebrate spinal reflexes. Kandel (1976) and his many associates completed a detailed analysis of the processes of habituation and sensitization in the Aplysia monosynaptic circuit. They were able to show that habituation was a presynaptic process involving a decrease in the probability of neurotransmitter release as a result of repeated activation. Similarly, a process of synaptic depression is responsible for habituation of the tail-flip escape response in the crayfish, another very productive invertebrate model system (Krasne 1969). In the Aplysia model, synaptic decrement is due to a persisting decrease in calcium ion influx into the terminals. Sensitization, elicited for example by strong shock to the tail of the animal, was due to activation of a polysynaptic circuit that acted presynpatically on the sensory neuron terminals, the same terminals that habituated. The effects on calcium channels are due in turn to complex and not fully understood biochemical cascades within the neurons. Kandel and associates have also described a long-term sensitization effect involving structural changes in the synapses that they have used as a model for long-term memory storage (Hawkins and Kandel 1984).

In the vertebrate spinal cord, the flexion reflex is polysynaptic. Thompson and Spencer (1966) were able to rule out any changes in excitability in the sensory neuron terminals and in the motor neurons themselves during habituation. However, sensitization did involve increases in motor neuron excitability, as noted above. They suggested, but could not prove, that a process of low-frequency depression in the interneurons was responsible for habituation, a process analogous to the presynaptic depression process demonstrated by Kandel and associates in Aplysia. Using a monosynaptic pathway in the isolated frog spinal cord, Farel and Thompson (1976) demonstrated a presynaptic process for habituation. The story concerning neuronal mechanisms of habituation is particularly satisfying because the same process of synaptic depression appears to underlie habituation in both invertebrate and vertebrate systems. This simple process of synaptic decrement can account for a wide range of behavioral phenomena of habituation.

The study of habituation continues to be a most active field of research, ranging from responses of nematode C. elegans (Wicks and Rankin 1996) to the startle response in mammals (Pilz and Schnitzler 1996) to behaviors in the human fetus and infant (Leader 1995, Kaplan et al. 1990).

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