Inhibition of the cutaneous eyeblink reflex by unilateral and bilateral acoustic input: the persistence of contralateral antagonism in auditory processing

The eyeblink reflex elicited by a cutaneous stimulus is inhibited by weak auditory stimuli that are heard just before the blink. It has been shown that monaural prestimuli produce more reflex depression than binaural prestimuli do, suggesting that reflex modification is sensitive to the outcome of antagonistic connections between contralateral auditory inputs. We examined the time course of this antagonism by giving unilateral versus bilateral pairs of noise pips 100 msec before the reflex eyeblink, with the noise pips separated by 0, 1, 4, or 8 msec. Unilateral stimuli were more effective in every condition, but their advantage diminished with increased delay between the two components. The extended bilateral and unilateral trends of increasing reflex depression with increased delay meet at about 15 msec; if this extrapolation is valid, 15 msec represents the upper limit on this system's retention of the location of a brief noise impulse. The rate of convergence of the two temporal functions reflects the decay of the antagonistic effect of one noise on its contralateral counterpart.     

Inhibition of the glabella reflex by monaural and binaural stimulation

The human eyeblink, elicited by a tap to the glabella, can be inhibited if a relatively weak acoustic signal precedes the tap by approximately 100 msec. The work reported here was designed to explore the surprising fact that more inhibition occurs when the acoustic prestimulation is presented monaurally than when it is presented binaurally. The present studies revealed that (a) given equally loud binaural inputs, a reduction of about 40 dB(A) in one of them is sufficient to produce inhibition comparable to that produced by a monaural signal, (b) the difference between nonaural and binaural inhibition remains constant as the intensity of prestimulation is varied, and (c) the simultaneous offset of a tone in one ear and onset of a tone in the other ear produces more inhibition than either monaural offest or onset alone. These findings suggest that the specific attributes of a given acoustic signal make independent contributions to the inhibition produced by that signal.     

Startle reflex inhibition in the rat: its persistence after extended repetition of the inhibitory stimulus

Startle reflexes to intense sound bursts are inhibited by weak stimuli that briefly precede their elicitation. In three experiments the startle stimulus (a 110-dB SPL tone burst) was presented 100 ms after the final link in a train of stimuli, the length of the train varying from 1 to 1,000, its repetition rate varying from 1 per s to 10 per s, and its constituents being 40 dB or 50 dB white noise bursts of 25 ms duration. Inhibition was invariant across train length and repetition rate. In a final experiment the startle stimulus was presented a variable interval after the final link, from 40 ms to 1280 ms, with 1 or 100 noise bursts (50 dB) in the train. Inhibition developed more rapidly following the last member of the 100-stimulus train, suggestive of a "priming" or sensitization effect of stimulus repetition, but its overall strength and subsequent rate of decay were not different in the two conditions. The general persistence of inhibition following these extended series of stimuli reveals that reflex inhibition must be the outcome of a fixed and obligatory process associated with sensory input.     

Temporal integration of acoustic and cutaneous stimuli shown in the blink reflex

Temporal integration of pairs of brief blink-eliciting acoustic and cutaneous stimuli was investigated to determine if there was integration of stimuli from different modalities. Reflexes elicited by a tone burst or by a brief electrical shock to the supraorbital nerve followed by a second tone burst or shock at short stimulus onset asynchronies (SOAs) were larger and faster than control reflexes elicited by a single stimulus identical to the lead stimulus of the stimulus pairs. Reflex amplitude was augmented at longer SOAs where there was no effect on latency. Temporal integration was evident for all stimulus pairs, showing that it is due, at least in part, to processes that occur outside specific sensory pathways. Heterogeneous stimulus pairs produced greater reflex enhancement than did homogeneous stimulus pairs. This finding was examined further in Experiment 2, which showed that reflex enhancement with pairs of acoustic pulses was unaffected by the frequency of the second stimulus, suggesting that sensory masking was not acting to suppress reflex expression with acoustic pulse pairs. Integration of reflexogenic acoustic stimuli shown in the blink reflex is restricted to shorter intervals than is integration of acoustic stimuli shown by psychophysical procedures, suggesting that the two methods reflect different aspects of stimulus processing. Integration of reflexogenic stimuli may result from summation of activity associated more directly with reflex expression than with perceptual awareness.     

Acoustic augmentation and inhibition of the human eyeblink

The human eyeblink elicited by a mechanically produced tap to the glabella was inhibited by a mild acoustic stimulus presented 200 msec prior to the tap and was augmented when the same acoustic stimulus was presented simultaneously with the tap. Monaural presentation of the acoustic stimulus prior to the tap yielded more reflex inhibition than when that same stimulus was presented binaurally. Binaural presentation of the acoustic stimulus simultaneously with the tap yielded more reflex augmentation than when that same stimulus was presented monaurally. These findings lend credence to the proposition that reflex inhibition and reflex augmentation are mediated by separate neural pathways.     

Modification of the human glabella reflex by antecedent acoustic stimulation

The eyeblink elicited by a mechanically produced tap to the glabella was inhibited by a 50-msec, 80-dB SPL tone presented in the interval 50 to 800 msec prior to the tap, but maximal inhibition occurred when the lead interval was 100 msec. At this lead interval, the amount of inhibition was an increasing function of prestimulus intensity, but reliable inhibition was detected when prestimulus intensity was only 30 dB SPL. With a given inhibitory prestimulus, the amount of inhibition was independent of the intensity of the blink-eliciting tap. Monaural presentation of a prestimulus was found to produce more inhibition than the binaural presentation of that same prestimulus. The offset of an otherwise continuous binaural acoustic signal 100 msec prior to a tap inhibited the eyeblink, but more inhibition was found when offset occurred in only one ear.     

Prepulse effects on magnitude estimation of startle-eliciting stimuli and startle responses

The present studies investigated the relationship between prepulse effects on the modification of the brainstem startle reflex and magnitude estimates of startle-eliciting stimuli. In Experiment 1, startle eyeblink responses were elicited in 24 students, half of whom were instructed to estimate the loudness of the startle stimulus (actual intensities of 80, 90, and 100 dB) and half of whom were instructed to estimate the magnitude of their eyeblink. When weak acoustic prepulses preceded the startle-eliciting stimulus, eyeblink amplitude was inhibited, and estimates of response magnitude decreased, but estimates of startle stimulus magnitude decreased only when 100-dB startle stimuli were presented. In Experiment 2, the same startle stimuli were preceded on some trials by a vibrotactile prepulse to the hand. In conditions in which startle amplitude was inhibited, startle stimulus magnitude estimates were not affected. This suggests that the effect of acoustic prepulses on 100-dB startle stimuli in Experiment 1 may have been due to loudness assimilation, an effect independent of the prepulse inhibition of startle responding.     

Spectral frequency and the modulation of the acoustic startle reflex by background noise

The rat's (Long-Evans) acoustic startle reflex to a high-frequency tone burst (10.5 kHz) was depressed by intense high-frequency band-pass noise (8-16 kHz) but enhanced by low frequency noise (1-2 kHz). However, contrary to the hypothesis that the depression of startle in intense background noise is produced by sensory masking, the reflex to a low-frequency tone burst (at 1 kHz) was depressed by both high- and low-frequency band-pass noise. Two additional hypotheses are offered to supplement sensory masking in order to explain the asymmetry in these data. The first is that the intratympanic reflex, which acts as a high pass filter on acoustic input, is elicited in intense backgrounds. The second is that acoustic startle reflexes elicited by intense low-frequency tones are in part elicited by their high-frequency distortion products and that these distortion products are then masked by high-frequency background noise.     

Reversal of motor learning in the vestibulo-ocular reflex in the absence of visual input

Motor learning in the vestibulo-ocular reflex (VOR) and eyeblink conditioning use similar neural circuitry, and they may use similar cellular plasticity mechanisms. Classically conditioned eyeblink responses undergo extinction after prolonged exposure to the conditioned stimulus in the absence of the unconditioned stimulus. We investigated the possibility that a process similar to extinction may reverse learned changes in the VOR. We induced a learned alteration of the VOR response in rhesus monkeys using magnifying or miniaturizing goggles, which caused head movements to be accompanied by visual image motion. After learning, head movements in the absence of visual stimulation caused a loss of the learned eye movement response. When the learned gain was low, this reversal of learning occurred only when head movements were delivered, and not when the head was held stationary in the absence of visual input, suggesting that this reversal is mediated by an active, extinction-like process.     

Tonal frequency shifts and gaps in acoustic stimulation as reflex-modifying events

When a relatively weak signal, such as a mild tone, precedes an intense reflex-eliciting stimulus by an appropriate interval (about 100 msec), the amplitude of the elicited reaction is often reduced. It was found that in student volunteers a brief gap in a steady pure tone that occurred 150 msec prior to a mild tap to the glabella (the flat region between the eyebrows) could inhibit the eyeblink elicited by the tap. It was also found that a shift in tonal frequency across a gap in a tone was more inhibitory than a gap with no frequency shift, but it was no more inhibitory than the onset of the short second tone alone. The final study determined the minimum amount of frequency shift required to produce an additional inhibitory effect above that of a gap alone. The findings are discussed in terms of various aspects of sensory processing.     

Human patellar reflex and conditioned reflex compared electromyographically

Inspite of continued work on the stretch reflex and “voluntary” movement study of the conditioned stretch reflex declined early in this century. The present experiments surveyed seven classical conditioning regimens for the human rectus femoris EMG seen after a blow to the patellar tendon. It was possible to (1) rule out conditioning to a knee touch that occured together with the tap, (2) establish weak conditioned stimulus, Sc, control for a tape recorder click and subsequent fist clench that preceded the tap by variable elapsed times, and (3) establish strong Sc control for a tone that sounded an invariant 0.27 sec before the tap. There were large differences, however, in Sc power across subjects, as measured by amplitude, latency, and frequency of conditioned EMG activity that occured prior to tap or when the tap was omitted. Purely reflexive responses, especially later EMG segments, also varied in amplitude and frequency, to support a conclusion that numerous controlling stimuli added or competed from trial to trial. Further disclosure of Sc contributions, including those from movement-generated stimulation, is warranted, especially for behaviors whose rhythmic timings, as in locomotion, might favor Pavlovian conditioning.     

The effect upon monaural sensitivity of continuous stimulation of the opposite ear

The threshold to a 1,000 c./sec. tone presented to the left ear was measured whilst the right ear was under continuous stimulation by a 400 c./sec. tone. Observations were made, on different groups of subjects, under three stimulus conditions and two conditions of attention. Thresholds were found to increase with increasing intensities of the continuous tone. Attention to that part of the field associated with the continuous stimulus produced no significant change, whether the continuous stimulus was present or not. There were no significant after-effects during ten minutes following the end of the continuous stimulus, though the results suggested a slow decrease in threshold.

Several explanations of the phenomenon are considered. Cross-hearing and the reflex contraction of the middle-ear muscles can be virtually excluded. Central inhibition or the central control of sensory end-organs can account for the results. A statistical hypothesis is also tenable.     

Blockade of GABAA receptors in the interpositus nucleus modulates expression of conditioned excitation but not conditioned inhibition of the eyeblink response

The cerebellum and related brainstem structures are essential for excitatory eyeblink conditioning. Recent evidence indicates that the cerebellar interpositus and lateral pontine nuclei may also play critical roles in conditioned inhibition (CI) of the eyeblink response. The current study examined the role of GABAergic inhibition of the interpositus nucleus in retention of CI. Male Long-Evans rats were implanted with a cannula positioned just above or in the anterior interpositus nucleus before training. The rats were trained with two different tones and a light as conditioned stimuli, and a periorbital shock as the unconditioned stimulus. CI training consisted of four phases: 1) excitatory conditioning (8 kHz tone paired with shock); 2) feature-negative discrimination (2 kHz tone paired with shock or 2 kHz tone concurrent with light); 3) summation test (8 kHz tone or 8 kHz tone concurrent with light); and 4) retardation test (light paired with shock) After reaching a criterion level of performance on the feature-negative discrimination (40% discrimination), 0.5 μl picrotoxin (a GABA_A receptor antagonist) was infused at one of four concentrations, each concentration infused during separte test sessions. Picrotoxin transiently impaired conditioned responses during trials with the excitatory stimulus (tone) in a dose-dependent manner, but did not significantly impact responding to the inhibitory compound stimulus (tone-light). The results suggest that expression of conditioned inhibition of the eyeblink conditioned response does not require GABAergic inhibition of neurons in the anterior interpositus nucleus.     

Blockade of GABAA Receptors in the Interpositus Nucleus Modulates Expression of Conditioned Excitation but not Conditioned Inhibition of the Eyeblink Response

The cerebellum and related brainstem structures are essential for excitatory eyeblink conditioning. Recent evidence indicates that the cerebellar interpositus and lateral pontine nuclei may also play critical roles in conditioned inhibition (CI) of the eyeblink response. The current study examined the role of GABAergic inhibition of the interpositus nucleus in retention of CI. Male Long-Evans rats were implanted with a cannula positioned just above or in the anterior interpositus nucleus before training. The rats were trained with two different tones and a light as conditioned stimuli, and a periorbital shock as the unconditioned stimulus. CI training consisted of four phases: 1) excitatory conditioning (8 kHz tone paired with shock); 2) feature-negative discrimination (2 kHz tone paired with shock or 2 kHz tone concurrent with light); 3) summation test (8 kHz tone or 8 kHz tone concurrent with light); and 4) retardation test (light paired with shock). After reaching a criterion level of performance on the feature-negative discrimination (40% discrimination), 0.5 microl picrotoxin (a GABAA receptor antagonist) was infused at one of four concentrations, each concentration infused during separate test sessions. Picrotoxin transiently impaired conditioned responses during trials with the excitatory stimulus (tone) in a dose-dependent manner, but did not significantly impact responding to the inhibitory compound stimulus (tone-light). The results suggest that expression of conditioned inhibition of the eyeblink conditioned response does not require GABAergic inhibition of neurons in the anterior interpositus nucleus.     

Habituation and dishabituation of the electrodermal orienting reflex in relation to extraversion and neuroticism

Orienting reflex (OR) habituation and dishabituation may be influenced by individual difference variables, including Eysenck's Extraversion (E) and Neuroticism (N) dimensions. Ninety subjects formed nine groups based on the crossover of high, medium, and low E and N. Each subject received, at each of two auditory stimulus intensities, two blocks of tone presentations. The last standard stimulus trial was followed by a novel stimulus and four repetitions of the standard stimulus. Using square root SCR, extraverts showed smaller initial response amplitudes than introverts at the low intensity of stimulation, while the reverse was true at high intensity. E and N were unrelated to SCR habituation rate. However, extraverts showed no dishabituation, while introverts did dishabituate.     

Modification of the human blink reflex by transient and sustained features of acoustic prestimulation

The effects of acoustic stimuli whose onsets and durations were controlled to vary their transient and sustained features on the size of a subsequently elicited blink reflex were examined in humans. Prestimuli both with and without transient features inhibited the reflex when they preceded the eliciting stimulus by brief lead intervals, showing that acoustic transients are sufficient, but not necessary, for reflex inhibition. Inhibition evoked by transient and sustained stimulus features showed partial summation, and inhibition evoked by stimuli with only transient and with transient and sustained features showed similar decay functions with increasing lead intervals. Blink augmentation was found at longer lead intervals early but not late in a session, and was more evident in women than men. Prestimuli with only transient features were more effective than those with both transient and sustained features, showing that sustained stimulus energy at the time of reflex elicitation is not only not necessary for blink augmentation, but also diminishes it.     

The fear potentiated startle effect. Blink reflex modulation as a result of classical aversive conditioning

A differential conditioning study examined whether an acoustic startle probe, presented during extinction of an aversively conditioned visual stimulus, potentiated the reflex eyeblink response in humans and whether this potentiation varied with the change in affective valence of the conditioned stimulus. Sixty college students were randomly assigned to view a series of two slides, depicting either unpleasant/highly arousing, unpleasant/moderate arousing, neutral/calm, pleasant/moderate arousing or pleasant/highly arousing scenes and objects (duration: 8 sec). During preconditioning (8 trials) and extinction (24 trials) acoustic startle probes (white noise bursts [50 ms; 95 dBA] were administered during and between slide presentation). During acquisition (16 trials) CS+ was reinforced by an electric shock. Startle response magnitudes significantly increased from preconditioning to extinction and were substantially larger to CS+. Conditioned startle reflex augmentation linearly increased with the pleasantness of the slides. Furthermore, subjects showed a greater post-conditioning increase of judged aversiveness to slides that they had previously reported to be more pleasant, exactly paralleling the startle reflex results.     

Acquisition of the classically conditioned eyeblink response in humans over the life span

Human subjects ranging in age from 18 to 85 years underwent classical conditioning of the eyeblink response to a tone conditioned stimulus (CS) and an air-puff unconditioned stimulus (UCS). There was a decline in percentage of conditioned responses with age. This decline was most noticeable in subjects over age 50. These conditioning deficits were not due to age-related changes in sensitivity to the tone CS or the air-puff UCS, nor could the conditioning deficits be attributed to an age-related decline in general cognitive abilities or to changes in spontaneous blink rates. The results are discussed in terms of using the classically conditioned eyeblink in humans in conjunction with the classically conditioned nictitating membrane response in rabbits as a model system for studying the neurobiology of age-related conditioning deficits.     

Cerebellum and conditioned reflexes

The central assumption of existing models of motor learning in the cerebellum is that cerebellar mossy fibres signal information about the context in which a movement is to be performed and climbing fibres signal in relation to a movement error. This leads to changes in the responsiveness of Purkinje cells, which on the next occasion will generate a corrected output in a given context. Support for this view has come mainly from work on adaptation of the vestibulo-ocular reflex. The discovery that classically conditioned eyeblink responses depend critically on the cerebellum offers the possibility to study the learning of a novel behaviour, rather than modification of an existing reflex. After repeated pairing of a neutral stimulus, such as a tone, with a blink-eliciting stimulus, the tone will acquire the ability to elicit a blink on its own. We review evidence from studies employing a wide variety of techniques that the cerebellum is critical in this type of learning as well as evidence that mossy and climbing fibres have roles assigned to them in cerebellar learning models.     

Fear develops to the conditioned stimulus and to the context during classical eyeblink conditioning in rats

In classical eyeblink conditioning, non-specific emotional responses to the aversive shock unconditioned stimulus (US), which are presumed to coincide with the development of fear, occur early in conditioning and precede the emergence of eyeblink responses. This twoprocess learning model was examined by concurrently measuring fear and eyeblink conditioning in the freely moving rat. Freezing served as an index of fear in animals and was measured during the inter-trial intervals in the training context and during a tone conditioned stimulus (CS) presented in a novel context. Animals that received CS-US pairings exhibited elevated levels of fear to the context and CS early in training that decreased over sessions, while eyeblink conditioned responses (CRs) developed gradually during acquisition and decreased during extinction. Random CS-US presentations produced a similar pattern of fear responses to the context and CS as paired presentations despite low eyeblink CR percentages, indicating that fear responding was decreased independent of high levels of learned eyeblink responding The results of paired training were consistent with two-process models of conditioning that postulate that early emotional responding facilitates subsequent motor learning, but measures from random control animals demonstrate that partial CS-US contingencies produce decrements in fear despite low levels of eyeblink CRs. These findings suggest, a relationship between CS-US contingency and fear levels during eyeblink conditioning, and may serve to clarify further the role that fear conditioning plays in this simple paradigm.