Somatosensory pain is not reliably modulated by weak acoustic stimuli.

BACKGROUND: Pain induced by electrical stimuli has been found in previous research to be reduced by brief, weak electrical pulses, termed prepulses, presented 40 to 60ms prior to the painful electrical stimulus. METHODS: The present experiment investigated the generality of this effect by presenting weak acoustic stimuli simultaneously with, or 80 or 1000ms prior to, painful electric shocks. In the second half of the experimental session, each participant (N=119) was told that the acoustic stimuli would either increase or decrease the pain induced by the electric shock, to investigate automatic and controlled cognitive processes in the modulation of pain. RESULTS: Acoustic stimuli presented simultaneously with painful stimulation increased pain slightly (4mm on a 100mm scale). Acoustic stimuli presented 80 and 1000ms prior to painful stimuli had no effect on pain. Information that acoustic stimuli would increase pain did so in females, but only when the acoustic stimulus was presented 80ms prior to the painful stimulus. CONCLUSIONS: The effect of the acoustic stimuli and of information was weak. Failure to replicate previous findings of decreased pain by weak prepulses was most likely due to the sensory modality of the prepulse stimuli. It is recommended that further studies of pain modulation by brief stimulation use electrical and not acoustic prepulse stimuli.

Caffeine-associated stimuli elicit conditioned responses: an experimental model of the placebo effect.

RATIONALE: A neutral stimulus repeatedly paired with administration of a drug may elicit a conditioned response. This process, termed pharmacological classical conditioning, may be important in the understanding of placebo effects. OBJECTIVE: The unconditioned response to caffeine is increased physiological and psychological arousal. The present study investigated whether stimuli associated with the use of caffeine, i.e. the smell and taste of coffee, elicited a conditioned increase in arousal. It was also investigated whether conditioned arousal modulated the unconditioned arousal induced by caffeine. METHODS: Twenty subjects who drank at least two cups of coffee per day were exposed to four conditions in a within-subjects design, where the subjects received coffee or orange juice crossed with placebo or 2 mg/kg caffeine. Dependent variables were skin conductance responses and startle reflexes to 85 dB noise bursts, skin conductance levels, blood pressure, heart rate, and subjective measures of arousal. RESULTS: Both caffeine (caffeinated juice) and caffeine-associated stimuli (decaffeinated coffee) increased subjective and physiological arousal. When caffeine and caffeine-associated stimuli were presented together (caffeinated coffee), a non-significant tendency towards an additive effect of the conditioned arousal on the unconditioned arousal to caffeine was seen in some dependent variables. CONCLUSIONS: Presentation of caffeine-associated stimuli to caffeine-users elicited conditioned responses similar to the unconditioned drug response. Thus, presentation of caffeine-associated stimuli could be used as an experimental model of placebo effects.

Inhibition of the human startle response is affected by both prepulse intensity and eliciting stimulus intensity.

The present study evaluated the effects of the intensity of prepulses and eliciting stimuli on the modification of the adult human acoustic startle eyeblink. Eyeblinks were elicited by 85, 95, and 105 dB(A) noise bursts, preceded a some trials by 60 or 70 dB(A) tones at a 120 ms stimulus onset asynchrony. Prepulse intensity was a within-subject variable in Experiment 1 (N = 19) and a between-groups variable in Experiment 2 (N = 38). For no-prepulse trials, as startle stimulus intensity decreased, startle amplitude, probability, and magnitude decreased, and startle latency increased. As startle stimulus intensity decreased from 105 to 95 dB, the amount of inhibition of response amplitude and magnitude remained stable for 70 dB prepulses in Experiment 1 and for both 60 and 70 dB prepulses in Experiment 2, whereas inhibition of response probability became more pronounced. As startle stimulus intensity decreased from 95 to 85 dB, prepulse inhibition of response amplitude and magnitude lessened and inhibition of response probability became still more pronounced in both experiments. These data show that the inhibition of startle can be affected by eliciting stimulus intensity, and that startle response amplitude and probability are affected by stimulus intensity changes in different ways.

A parametric study of the separate contributions of the tactile and acoustic components of airpuffs to the blink reflex.

Airpuffs are often used as blink reflex eliciting stimuli, but the airpuff makes an abrupt noise when it leaves the tube. The present study investigated the effects of the tactile and acoustic components of airpuffs on the blink reflex in 18 human subjects. Subjects received airpuffs to the temple at 10.3, 20.7 and 31.0 kPa in a within-subjects design. The airpuff-associated noise was attenuated (Airpuff + Attenuated noise) or airpuffs were presented without noise-attenuation (Airpuff+ Unattenuated noise) in two conditions. In the third condition, the airpuff was directed away from the temple to eliminate the tactile component of the airpuff (Noise alone). Reflexes were larger, more probable and faster to the Airpuff+ Unattenuated noise compared to the Airpuff+ Attenuated noise. This indicates that there is an excitatory influence from the acoustic component of the airpuff. The findings suggest that researchers should reduce the acoustic component of airpuffs in studies that use airpuffs as reflex eliciting stimuli.

The effect of acoustic pulse intensity upon the electrically elicited blink reflex at positive and negative stimulus onset asynchronies.

The present study examined the effects of acoustic pulse intensity and stimulus onset asynchrony (SOA) on the electrically elicited startle reflex response. Subjects were presented with 165 startle eliciting stimuli: 15 control trials with no acoustic pulse, and 5 trials at each pulse intensity (50, 70, and 90 dB) for each SOA (-80, 60, -40, -20, 0, 20, 40, 60, 80, and 100 ms). The results demonstrated R2 magnitude facilitation at negative, simultaneous, and short positive SOAs. R2 facilitation was greatest in the 90 dB condition and least in the 50 dB condition. R1 facilitation at short positive SOAs was greater for more intense acoustic pulses. These data support the notion that R2 facilitation at near-zero SOAs may be the result of combination of pulse induced potentiation of the electrically elicited startle response and temporal summation of the effects of electrical and acoustic stimuli at the facial motor nucleus.

Attentional modulation of blink startle at long, short, and very short lead intervals.

The present research investigated attentional blink startle modulation at lead intervals of 60, 240 and 3500 ms. Letters printed in Gothic or standard fonts, which differed in rated interest, but not valence, served as lead stimuli. Experiment 1 established that identifying letters as vowels/consonants took longer than reading the letters and that performance in both tasks was slower if letters were printed in Gothic font. In Experiment 2, acoustic blink eliciting stimuli were presented 60, 240 and 3500 ms after onset of the letters in Gothic and in standard font and during intertrial intervals. Half the participants (Group Task) were asked to identify the letters as vowels/consonants whereas the others (Group No-Task) did not perform a task. Relative to control responses, blinks during letters were facilitated at 60 and 3500 ms lead intervals and inhibited at the 240 ms lead interval for both conditions in Group Task. Differences in blink modulation across lead intervals were found in Group No-Task only during Gothic letters with blinks at the 3500 ms lead interval facilitated relative to control blinks. The present results confirm previous findings indicating that attentional processes can modulate startle at very short lead intervals.

The effects of different doses of caffeine on habituation of the human acoustic startle reflex.

Research in this laboratory showed that caffeine (4 mg/kg) delays habituation of the acoustic startle reflex in humans. The present study examined the effects of 2- and 6-mg/kg doses of caffeine on acoustic startle habituation in moderate-high and low caffeine users. Eyeblink responses to 30 trials of 85-dB noise stimuli were measured beginning 30 min after oral ingestion of either placebo or 2 or 6 mg/kg of caffeine. The 2-mg/kg dose of caffeine delayed startle habituation in both moderate-high and low caffeine users. The 6-mg/kg dose produced no differential effects on startle responding from placebo. In moderate-high users, following habituation, startle responding was smaller in the placebo condition compared to both caffeine conditions. In low users there were no differences in posthabituation responding between doses, suggesting that this dose effect is dependent on a history of chronic caffeine usage.

The effects of caffeine and directed attention on acoustic startle habituation.

The present experiment tested the effects of caffeine on acoustic startle habituation during different attention tasks in which subjects either (a) attended to the acoustic startle stimulus (auditory attention; n = 9) (b) attended to a visual search task during presentation of acoustic startle stimuli (visual attention; n = 10), or (c) were given no specific instructions during acoustic startle testing (no attention; n = 9). Startle eyeblink responses were measured after subjects received either caffeine (1 mg/kg) or placebo. Caffeine significantly delayed response habituation in the no attention group and in the auditory attention group, but had no effect on habituation in the visual attention group. These data show that startle habituation can occur with minimal attention being directed to the acoustic startle stimulus, and that visual attention cancels the effects of caffeine on startle habituation.

Effects of caffeine and caffeine-associated stimuli on the human startle eyeblink reflex.

An experiment was performed (n = 19) that investigated the effect of caffeine and expectancy of caffeine on the eyeblink component of the startle reflex. Nineteen habitual caffeine users received caffeinated coffee, caffeinated juice, decaffeinated coffee, or decaffeinated juice in four sessions spaced 1 week apart. Twenty-five to 30 min after ingestion of the liquid, 30 acoustic startle stimuli were presented. The results showed that caffeine increased startle eyeblink amplitude. Startle reflex onset latency was significantly longer in the decaffeinated coffee condition than in the other three conditions. This may have been due to the activation of a compensatory slowing of the reflex by the anticipation of caffeine, a slowing that was then overridden by caffeine speeding the response.

Startle eyeblink elicitation in attention deficit disordered children using low-intensity acoustic stimuli.

The acoustic startle eyeblink response was measured in 11 pediatric psychiatric inpatients, 7 diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) and 4 diagnosed with other conditions (non-ADHD). Startle stimuli were 85 or 95 dB SPL, 50-msec. noise pulses. Startle eyeblink responses were reliably measured for all children. Startle response latency was faster for ADHD children than for clinical control subjects in all stimulus conditions. These data show that the acoustic startle eyeblink response can be reliably elicited in ADHD children at lower intensities (85-95 dB) than those used in previous published research (104 dB). This may increase the use of the startle paradigm, since less intense stimuli may be less disturbing to the children, increasing compliance and allowing longer testing sessions.

The use of next-of-kin in assessing handedness.

The present study administered a 15-item handedness questionnaire to 129 college students and their next-of-kin. This questionnaire was similar to the Edinburgh Handedness Inventory, except that a 7-point scale was used instead of a 2-choice scale. Test-retest reliability was evaluated with a second administration of the handedness questionnaire to each subject. Analysis showed a high test-retest reliability for all items and a high correlation between subjects and next-of-kin responding for most items. However, some items on the Edinburgh Handedness Inventory showed much higher correlations than others when comparing subject and next-of-kin responding. The contribution of these data is that subjects' handedness can be accurately estimated from next-of-kin responses if a subset of these questionnaire items are used.

On threat of shock as an elicitor of anxiety: a methodological note.

The effects of anxiety on the eyeblink component of the human startle response were measured in 32 college students. The manipulation of threat of shock was not successful in eliciting anxiety, suggesting that, while threat of shock can increase anxiety, this increase is not inevitable, illustrating the importance of a manipulation check of the effectiveness of the threat.

Directed attention influences the modification of startle reflex probability.

The present study was designed to investigate the effect of directed attention on elicitation and modification of the startle reflex. 30 adult human subjects received 90 dB(A) broadband noise startle stimuli either alone or preceded by a 60 dB(A) prepulse (either 2000-Hz tone, 1000-Hz tone, or broadband noise). Subjects were instructed to attend to one of the three prepulses during half the trials and to ignore all stimuli during the rest of the trials. The probability of responding while attending to a prepulse was significantly lower than the probability of responding while ignoring the prepulses. Responding to the prepulses was also more probable while subjects were attending to the prepulses, and these effects were more pronounced for tone than for noise prepulses. These results suggest that directed attention can influence the probability of the startle reflex without influencing startle amplitude or latency.

Cardiopulmonary baroreceptors affect reflexive startle eye blink.

Baroafferent signals originating from the 'high pressure' arterial vascular system are known to impact reflexive startle eye blink responding. However, it is not known whether baroafferent feedback of the 'low pressure' cardiopulmonary system loading status exerts a similar effect. Lower Body Negative Pressure (LBNP) at gradients of 0, -10, -20, and -30mm Hg was applied to unload cardiopulmonary baroreceptors. Acoustic startle noise bursts were delivered 230 and 530ms after spontaneous R-waves, when arterial baroreceptors are either loaded or unloaded. Eye blink responses were measured by EMG, and psychomotor reaction time by button pushes to startle stimuli. The new finding of this study was that unloading of cardiopulmonary baroreceptors increases startle eye blink responsiveness. Furthermore, we replicated the effect of relative loading/unloading of arterial baroreceptors on startle eye blink responsiveness. Effects of either arterial or cardiopulmonary baroreceptor manipulations were not present for psychomotor reaction times. These results demonstrate that the loading status of cardiopulmonary baroreceptors has an impact on brainstem-based CNS processes.

Prepulse inhibition of the startle eyeblink as an indicator of temporal summation.

The inhibition of the human startle eyeblink response was assessed in three experiments in which the duration of the prepulse was manipulated. In all cases, inhibition of startle was more pronounced as prepulse duration increased from 6 to 50 msec. Inhibition of startle amplitude for single prepulses was not significantly different from that for paired prepulses (Experiment 1), but inhibition was more pronounced as prepulse intensity increased (Experiment 3). Varying the interval between prepulse offset and startle-stimulus onset had no significant effect on inhibition (Experiment 2). These data demonstrate the sensitivity of startle inhibition to prepulse duration, and suggest that this response system can be used to evaluate early temporal summation in the auditory system.

Prepulse inhibition decreases as startle reactivity habituates.

In the present study, I investigated the effect of stimulus repetition on human startle eyeblink reflex inhibition (PPI) by a prepulse. Participants were assigned to one of three groups (n = 14 each), in which they received 18 trials of (a) noise startle stimuli presented alone or preceded by 1000-Hz tone prepulses, (b) startle stimuli presented alone, or (c) prepulses presented alone. All participants then received 18 more trials of startle stimuli presented alone or preceded by 1000-Hz tone prepulses, followed by 6 trials of startle stimuli presented alone or preceded by 2000-Hz tone prepulses. As trials progressed, startle eyeblink electromyogram magnitude habituated and PPI decreased. PPI was not affected by the repeated presentation of the prepulses alone but decreased with the repeated presentation of the startle stimulus alone. Changes in the frequency of the prepulse had no significant effect on PPI. These data suggest that the reduction of PPI that is seen across trials is not due to habituation of the prepulse but is related to startle reactivity in control trials, which is reduced by habituation.

Signal attenuation as a function of integrator time constant and signal duration.

In some laboratories, eyeblink electromyogram is rectified and smoothed before the analog signal is digitized. The relationship among the integrator time constant, the duration of the response, and the attenuation of the data was investigated by passing a number of signals at durations of 5, 10, 20, 50, and 100 ms into a contour-following integrator (Coulbourn model S76-01), which first rectifies and then smooths (integrates) the signal. Integrator time constants of 10, 42, 70, 144, and 300 ms were used. The output of the integrator was sampled (1,000 Hz) and stored on a Macintosh SE computer. The integrator attenuated the signal, and the amount of attenuation increased as the duration of the signal decreased and as the time constant of the integrator increased. For brief inputs, the integrator does not charge fully, so only the early portion of the charge limb is present, and this early portion is the steepest part of the charge limb. Therefore, the longer the time constant, the less likely that small or brief responses will be detected.

The startle eyeblink response to low intensity acoustic stimuli.

Four experiments were conducted to investigate the acoustic startle response to stimuli of low intensities. Eyeblink responses (integrated EMG from orbicularis oculi) were measured from male and female college students. Experiment 1 compared tone and noise stimuli varying in intensity (50 and 60 dB(A) SPL), with noise stimuli producing greater response amplitude and probability than tone stimuli. Experiment 2 was designed to investigate temporal summation of low intensity stimuli using single and paired 70dB(A) SPL broadband noises, and an onset-to-onset interval between the brief stimuli in a pair equal to the duration of the single stimuli. Increasing the duration of single stimuli resulted in larger responses, illustrating temporal summation. Experiment 3 used 60 and 70 dB(A) SPL broadband noise varying in rise/fall time, with faster-rising stimuli producing larger responses, and more intense stimuli producing larger and more probable responding. Experiment 4 employed the startle modification paradigm using 60 and 70 dB(A) SPL broadband noises as startle stimuli and a 50dB(A) SPL tone as a prepulse. Response amplitude and probability to both 60 and 70 dB(A) SPL stimuli were significantly inhibited by the 50dB(A) SPL prepulse. These studies show that the acoustic startle response is more sensitive than previously thought, and the elicitation of startle by low intensity stimuli argues against the limitation of the startle reflex as a high intensity phenomenon. These findings can increase the application of this response system by showing that startle stimuli need not be of high intensity, because reliable and differential startle can be elicited and modified at relatively low stimulus intensities.

Prepulse rise time and startle reflex modification: different effects for discrete and continuous prepulses.

The rise time of an auditory prepulse was varied to determine whether the onset transient of the prepulse is of primary importance in the modification of the acoustic startle reflex. In Experiment 1, 20-ms long discrete prepulses were presented at a lead time of 150 ms, and prepulse rise time was varied from 0.1 to 20 ms. Although all prepulses resulted in decreased response amplitude (inhibition of startle), varying rise time from 0.1 to 20 ms had no effect on reflex modification. These results suggest that the startle response is not sensitive to prepulse rise time changes in the range used here. In Experiment 2, continuous prepulses (in which lead time equals duration) were presented. Several of these prepulses had a lead time of 150 ms and rise times ranging from 0.1 to 150 ms, whereas others had a rise time of 0.1 ms and lead times of 50 to 150 ms. The results showed that only the fast-rising, 50-ms lead time prepulse decreased response amplitude, with the other prepulses having no effect on amplitude, relative to control responding. Rise time changes generally had no effect on responding, but responses were larger at longer lead times than at shorter lead times. Response probability was inhibited by fast-rising prepulses at lead times of 50 to 130 ms. Together with the results of Experiment 1, these findings suggest that startle reflex inhibition is determined by the onset of a prepulse, and that this inhibition is not sensitive to small changes in prepulse rise time.(ABSTRACT TRUNCATED AT 250 WORDS)

The startle response and auditory temporal summation in neonates.

The present study assessed temporal summation of transient and sustained stimuli in the startle eyeblink response system in neonates during quiet sleep. Subjects received 100-dB(A), fast-rising broadband noise bursts of two types: (a) single stimuli varying in duration from 20 to 100 ms and (b) pairs of 3-ms bursts presented at interpulse intervals corresponding to the single-stimulus durations. In addition, a single 3-ms pulse was used as an anchor point for both stimulus types. For startle amplitude, single stimuli were more effective than were paired stimuli, but the temporal summation functions were similar for the two types of stimuli. Response amplitude increased as stimulus duration/interval increased to 50 ms, but not beyond. For startle probability, temporal summation was similar for single and paired stimuli at 20 ms. Pairs of pulses were equally effective at 20, 35, and 50 ms, beyond which the second pulse was not effective. Increasing the duration of single stimuli from 20 to 35 ms resulted in increased probability, illustrating a contribution of sustained summation beyond that of transient summation. Response latency was generally greater for paired than for single stimuli. The results suggest that temporal summation of brief stimuli is deficient in the neonate. These data were compared to adult data from an analogous study, and suggest that the transient system is immature in infants, and that this immaturity is expressed differently by startle amplitude, probability, and latency.