Anxiety and initial value dependence in startle habituation.

Studies suggest that deficits in startle reflex habituation occur in trait and clinical anxiety. Measures of habituation are affected by the magnitude of the initial response, with larger initial responses predicting a steeper decline in response over repeated trials. This relationship between initial value and change, commonly called the Law of Initial Value or initial value dependence (IVD), has been partialled out as a covariate in habituation research, but variation in IVD may be informative in itself, reflecting differences in physiological reactivity. The present study explored how trait anxiety and contextual anxiety relate to habituation kinetics of the startle eyeblink response: initial value, linear habituation slope, and the relationship between them (IVD). Participants (n = 31; 15 Control, 16 Contextual Anxiety [CA]) were exposed to two blocks of acoustic startle stimuli, and CA participants were warned that they may receive an electrical shock to the wrist during block 2. Trait anxiety did not predict habituation slope, but it did predict a weaker IVD relationship, meaning that high initial startle magnitude was less predictive of a steep response decline in trait-anxious subjects. Meanwhile, CA did not impact startle habituation or IVD. The results suggest that individual differences in trait anxiety are related to the relationship between initial physiological response magnitude and subsequent change in response. IVD in startle habituation may thus serve as a better biomarker of healthy emotional responding than startle habituation per se.

Efficacy of stimulus intensity increases and decreases as inhibitors of the acoustic startle response.

The human startle eyeblink response can be inhibited by a change in the stimulus environment briefly before the startling stimulus; both stimulus presentation (prepulse) and cessation of background sound (gap) can result in startle inhibition. More intense prepulses often result in greater inhibition, and this study (N = 53 college students) examined whether graded decreases in sound energy relative to a steady background noise (a "partial gap") would follow this same pattern of inhibition. Embedded in a 65 dB steady background noise were 100 dB white noise startle stimuli preceded at 120 ms on some trials by stimulus intensity increases or decreases of 5, 10, or 15 dB relative to background. Results showed that startle inhibition was graded by amount of change relative to background, such that greater increases or decreases resulted in greater inhibition. Also, increases were more effective startle inhibitors than decreases at equivalent levels of change from background. These results demonstrate that the neural centers responsible for startle inhibition are responsive to both increases and decreases in stimulus intensity, and are sensitive to amount of change, not simply whether a change occurs. These findings may have implications for the development of a screening method for a hearing disorder called tinnitus.

Presidential Address 2014: The more-or-less interrupting effects of the startle response.

The startle response can be used to assess differences in a variety of ongoing processes across species, sensory modalities, ages, clinical conditions, and task conditions. Startle serves defensive functions, but it may also interrupt ongoing processes, allowing for a reorientation of resources to potential danger. A wealth of research suggests that prepulse inhibition of startle (PPI) is an indicator of the protection of the processing of the prepulse from interruption by the startle response. However, protection against interruption by suppressing the startle response may extend to many other ongoing processes, including the higher processing of the startle stimulus itself. Proof of protection would require measuring ongoing processing, which has very rarely been reported. The idea that PPI represents the protection of the earliest stages of prepulse processing can be challenged, since those earliest stages are completed by the time the startle response occurs, so they are not threatened by interruption and need not be protected. The conception of low PPI as indicative of a "gating deficit" in schizophrenia should be made with caution, since low PPI is seen in some, but not all studies of schizophrenia, but also in a range of other disorders and conditions. Finally, startle is often used to probe ongoing processes, but the response also modifies those processes, interrupting some processes but perhaps facilitating others. A deeper understanding of the function of startle and PPI might improve the precision of application of these measures in the investigation of a range of research topics.

Effects of anxiety sensitivity and expectations on the modulation of the startle eyeblink response during a caffeine challenge.

RATIONALE: The way in which the tendency to fear somatic arousal sensations (anxiety sensitivity), in interaction with the created expectations regarding arousal induction, might affect defensive responding to a symptom provocation challenge is not yet understood. OBJECTIVES: The present study investigated the effect of anxiety sensitivity on autonomic arousal, startle eyeblink responses, and reported arousal and alertness to expected vs. unexpected caffeine consumption. METHODS: To create a match/mismatch of expected and experienced arousal, high and low anxiety sensitive participants received caffeine vs. no drug either mixed in coffee (expectation of arousal induction) or in bitter lemon soda (no expectation of arousal induction) on four separate occasions. Autonomic arousal (heart rate, skin conductance level), respiration (end-tidal CO2, minute ventilation), defensive reflex responses (startle eyeblink), and reported arousal and alertness were recorded prior to, immediately and 30 min after beverage ingestion. RESULTS: Caffeine increased ventilation, autonomic arousal, and startle response magnitudes. Both groups showed comparable levels of autonomic and respiratory responses. The startle eyeblink responses were decreased when caffeine-induced arousal occurred unexpectedly, e.g., after administering caffeine in bitter lemon. This effect was more accentuated in high anxiety sensitive persons. Moreover, in high anxiety sensitive persons, the expectation of arousal (coffee consumption) led to higher subjective alertness when administering caffeine and increased arousal even if no drug was consumed. CONCLUSIONS: Unexpected symptom provocation leads to increased attention allocation toward feared arousal sensations in high anxiety sensitive persons. This finding broadens our understanding of modulatory mechanisms in defensive responding to bodily symptoms.

Support for the interruption and protection hypotheses of prepulse inhibition of startle: evidence from a modified Attention Network Test.

The startle response may interrupt information processing (interruption hypothesis), and prepulse inhibition of startle (PPI) may protect that processing from interruption (protection hypothesis). These hypotheses were tested by measuring startle eyeblinks during an Attention Network Test (ANT), a combined flanker and cue reaction time (RT) task that measures the efficiency of multiple attentional networks. ANT trials with and without startle stimuli presented in the interval between the visual cue (prepulse) and target were compared. Results showed that the startle stimulus served as an alerting stimulus, speeding RT in the ANT. However, this reaction time speeding was most pronounced on trials with no startle response (100% PPI). This suggests that the alerting effect of the startle stimulus was attenuated by the startle response, and that PPI decreased the degree of this interference, in support of the interruption and protection hypotheses.

Effects of a startle stimulus on response speed and inhibition in a go/no-go task.

Two studies examined the interaction of an acoustic startle stimulus and visual go/no-go task stimuli on startle reactivity and task performance. In the first study, an acoustic stimulus (50 ms, 100 dB noise) was presented alone or with a green (go) or red (no-go) circle; in the second study, a prepulse (50 ms, 75 dB noise) was presented alone or 120 ms before the startle stimulus or circle. The startle stimulus speeded responses to the go stimuli and increased the covert false alarm rate in the no-go condition (measured by EMG activity in the hand), although very few overt errors were made in the no-go condition. Startle response magnitude was increased by a circle but decreased by a prepulse. The speeding of go responses caused by a startle stimulus was attenuated by the occurrence of a startle response, suggesting that an intense accessory stimulus can facilitate responding to an imperative stimulus, and that the startle response to that intense stimulus can interfere with that facilitation.

Rapid cortisol enhancement of psychomotor and startle reactions to side-congruent stimuli in a focused cross-modal choice reaction time paradigm.

The stress hormone cortisol has been shown to affect hemodynamic activity of human brain structures, presumably via a nongenomic mechanism. However, behavioral implications of this finding remain unknown. In a placebo-controlled, blinded, cross-over design the rapid effects of IV hydrocortisone (5mg) on cross-modal integration of simultaneous, unilateral visual and acoustic signals in a challenging startle and reaction time (RT) paradigm were studied. On two separate days 1 week apart, 24 male volunteers responded by button push to either up- or down pointing triangles presented in random sequence in the periphery of one of the visual hemi-fields. Visual targets were accompanied by unilateral acoustic startle noise bursts, presented at the same or opposite side. Saccadic latency, manual RT, and startle eye blink responses were recorded. Faster manual reactions and increased startle eye blink responses were observed 11-20 min after hydrocortisone administration when visual targets and unilateral acoustic startle noises were presented in the same sensory hemi-field, but not when presented in opposite sensory hemi-fields. Our results suggest that a nongenomic, cortisol-sensitive mechanism enhances psychomotor and startle reactions when stimuli occur in the same sensory hemi-field. Such basic cognitive effects of cortisol may serve rapid adaptation and protection against danger stimuli in stressful contexts.

Acoustic startle reactivity while processing reward-related food cues during food deprivation: evidence from women in different menstrual cycle phases and men.

Previous research has shown that food deprivation enhances the acoustic startle reflex when it is elicited during presentation of visual food cues. Frustrative nonreward may explain this effect, since visual food cues are also rated to be more appetitive and arousing during food deprivation. However, the impact of menstrual cycle and sex on this effect remains unclear, and it is also not known whether this effect is influenced by hunger and motivation to eat. According to a within-study design, 20 healthy women in different menstrual cycle phases and 14 healthy men participated twice, in normal and food-deprived conditions. After 18 h of food deprivation, acoustic startle was attenuated by appetitive nonfood foreground pictures, but enhanced by presentation of food pictures. No differences between menstrual cycle phases and sexes appeared. The effect correlated with hunger changes, suggesting that motivational factors play a role.

Startle effects on saccadic responses to emotional target stimuli.

Startle stimuli elicit various physiological and cognitive responses. This study investigated whether acoustic startle stimuli affect saccadic reactions in an emotional pro- or antisaccade task. Startle probes were presented either 500 ms before or simultaneous with an imperative stimulus that indicated whether a saccade towards or away from positive, neutral, or negative peripheral target pictures had to be performed. Valence interacted with saccade direction according to an approach-avoidance pattern of gaze behavior, with delayed prosaccades to negative targets and antisaccades away from positive targets. Acoustic startle stimuli preceding the presentation of peripheral target pictures speeded up the initiation saccades, irrespective of stimulus valence. Results indicate a speeding of cognitive-motor processing by preceding startle stimuli.

Maternal social stress modulates the development of prepulse inhibition of startle in infants.

BACKGROUND: Stress during rearing has negative effects on the maturation of information processing in rodent offspring, but similar evidence in humans is absent. Prepulse inhibition (PPI) of startle is a measure reflecting the integrity of information processing. PPI does not depend on active cooperation, making it a suitable measure for studying newborns and infants. This study investigated whether postnatal development of infant PPI is influenced by self-reported stress in the mother. METHODS: 49 healthy term-born infants were studied twice, four days after birth and again at four months. PPI was assessed by presentation of acoustic startle stimuli (95dB) either alone or preceded (SOA 120ms) by a prepulse (75dB). Mother's social stress levels were assessed with the modified Trier Inventory for the Assessment of Chronic Stress (TICS). Cortisol saliva samples were collected from mothers and their children. RESULTS: ANOVA revealed a different development of PPI in infants whose mothers reported enhanced stress levels due to social isolation and reduced social recognition. Cortisol levels were related to mothers' self-report stress, but not to PPI development in infants. CONCLUSIONS: Maternal stress experience has an impact on the maturation of human infants' information processing in the first four months after birth.

Cold pressor stress affects cardiac attenuation of startle.

Stress may affect cardio-afferent neural traffic. We investigated whether acute autonomic stress has an impact on cardiac modulation of startle (CMS), a 'background' methodology for assessing baro-afferent signal transmission. Therefore, 38 healthy volunteers received acoustic startle stimuli (105 dB) at 6 different latencies relative to the R-wave (R +0, 100, 200, 300, 400, and 500 ms; randomized order), both before and immediately after either a cold pressor (n = 19) or a control intervention (n = 19). Blood pressure was enhance d significantly in the cold pressor group right after the intervention (+13.7/5.7 mmHg), reflecting sustained autonomic activation after the stress procedure. Before stress, startle responses were lowest for latencies of R +200 and +300 ms, corroborating previous findings. After the cold pressor test, startle responsiveness was lowest for earlier latencies (R +0, +100 and +200 ms). Stress facilitation of pre-ejection baro-afferent traffic originating from atrial mechano-sensitive receptors may be associated with this time shift effect. We conclude that the cardiac modulation of startle is sensitive to altered temporal baro-afferent feedback characteristics induced by stress and autonomic activation.

Pre- and perinatal predictors of startle eye blink reaction and prepulse inhibition in healthy neonates.

The present study examined the startle eye blink reflex and prepulse inhibition (PPI) in 65 healthy term-born neonates. Although the startle eye blink is already present at birth, some relevant neuronal structures are not fully mature. We therefore investigated the relationship between prenatal maturation and perinatal stress experience on startle eye blink and PPI. Eye blinks were evoked by unilaterally presented acoustic broadband white noise (50 ms, 95 dB, prepulse 75 dB). Startle response magnitude and percent PPI were calculated for ipsilateral and contralateral side of stimulation. Neonates exhibited stronger startle responses ipsilaterally than contralaterally, and a significant PPI. Neonates with more prenatal growth and less perinatal stress had greater startle magnitudes. Neonates with more stress had more PPI contralaterally. Results suggest that startle eye blinks may be useful as indicators of prenatal maturation and perinatal stress.

Failure to sustain prepulse inhibition in adolescent marijuana users.

BACKGROUND: Marijuana use is typically initiated during adolescence, which is a critical period for neural development. Studies have reported reductions in prepulse inhibition (PPI) among adults who use marijuana chronically, although no human studies have been conducted during the critical adolescent period. METHODS: This study tested PPI of acoustic startle among adolescents who were either frequent marijuana users or naïve to the drug (Controls). Adolescents were tested using two intensities of prepulses (70 and 85 dB) combined with a 105 dB startle stimulus, delivered across two testing blocks. RESULTS: There was a significant interaction of group by block for PPI; marijuana users experienced a greater decline in the PPI across the testing session than Controls. The change in PPI of response magnitude for users was predicted by change in urine THC/creatinine after at least 18 h of abstinence, the number of joints used during the previous week before testing, as well as self-reported DSM-IV symptoms of marijuana tolerance, and time spent using marijuana rather than participating in other activities. CONCLUSIONS: These outcomes suggest that adolescents who are frequent marijuana users have problems maintaining prepulse inhibition, possibly due to lower quality of information processing or sustained attention, both of may contribute to continued marijuana use as well as attrition from marijuana treatment.

Cardiac modulation of startle: effects on eye blink and higher cognitive processing.

Cardiac cycle time has been shown to affect pre-attentive brainstem startle processes, such as the magnitude of acoustically evoked reflexive startle eye blinks. These effects were attributed to baro-afferent feedback mechanisms. However, it remains unclear whether cardiac cycle time plays a role in higher startle-related cognitive processes, as well. Twenty-five volunteers responded first by 'fast as possible' button pushes (reaction time, RT), and second, rated perceived intensity of 60 acoustic startle stimuli (85, 95, or 105 dB; 50 ms duration; binaural; instantaneous rise time), which were presented either 230 or 530 ms after the R-wave, and eye blink responses were measured by EMG. RT was divided into evaluation and motor response time according to previous research. Increasing stimulus intensity enhanced startle eye blink, intensity ratings, and RT components. Eye blinks and intensity judgments were lower when startle was elicited at a latency of R+230 ms, but RT components were differentially affected: the evaluative component was attenuated, and the motor component was accelerated when stimuli were presented 230 ms after the R-wave. We conclude that the cardiac cycle affects the attentive processing of acoustic startle stimuli.

Physiologic responses to racial rejection images among young adults from African-American backgrounds.

Physiologic reactivity to racially rejecting images was assessed in 35 young adults (10 males, 25 female) from African-American backgrounds using the startle probe paradigm. In a laboratory setting, participants viewed 16 images depicting racial rejection, racial acceptance, nonracial negative, and nonracial positive themes. While viewing these images, startling bursts of noise were presented and the magnitude of the eyeblink responses were measured. Results supported an attentional mechanism which suggests that, while viewing both racially rejecting and nonracial positive images, individuals may be so absorbed in processing the images that they appear less distracted by the startling noise. However, these patterns were only found for participants low in racial regard. Young adults who felt positively about their racial background did not exhibit differential processing of startle stimuli as a function of slide themes. Race-rejection sensitivity did not moderate startle reactivity. Developmental implications, particularly in light of coping with racial discrimination, are discussed.

Lateralization effects on the cardiac modulation of acoustic startle eye blink.

Cardiac modulation of startle eye blink has been introduced as a methodology to reflect baro-afferent signal transmission. Recent studies showed that affective startle modulation is specific to left-ear presentation that may be due to hemispheric specificity in processing emotional-relevant stimuli, similar to the processing of visceral- and baro-afferent stimuli. To explore whether cardiac modulation of startle eye blink is lateralized as well, 37 healthy volunteers received 160 unilateral acoustic startle probes of 105 dB(A) intensity presented to both ears, one at a time. They were elicited 0, 100, 230, and 530 ms after the R-wave of the cardiac cycle. Startle response magnitude was significantly diminished at a latency of 230 ms, which may be due to the baro-afferent neural feedback at this temporal location, but only for left-ear presentation. This lateralization effect in the cardiac modulation of startle eye blink may reflect the previously described advantages of right-hemispheric brain structures in relaying viscero- and baro-afferent signal transmission.

Endogenous cortisol suppression with metyrapone enhances acoustic startle in healthy subjects.

Previous human studies have shown that excess cortisol sufficient to fully occupy central nervous system (CNS) corticosteroid receptors may reduce startle eye blink. The present study tested whether cortisol depletion and the resulting reduction in activity of CNS corticosteroid receptors has the opposite effect. In a single-blind, placebo-controlled, randomized study, eye blink EMG responses to 105 dB acoustic startle stimuli were assessed in 25 healthy subjects who received oral metyrapone (1500 mg) to suppress endogenous cortisol production, while 24 controls received oral placebo. As expected, metyrapone significantly reduced salivary cortisol, indicating effective endogenous cortisol suppression. Startle eye blink responses were significantly increased in the metyrapone group. Short-term habituation of the startle reflex was not different between groups. Our results suggest that startle is enhanced during depletion of cortisol. This effect may be mediated by CNS mechanisms controlling cortisol feedback.

Impact of stimulus signal-to-noise ratio on prepulse inhibition of acoustic startle.

Prepulse inhibition (PPI) of the human acoustic startle response is reduced in the presence of background noise of a sufficient intensity, possibly due to a reduction in signal-to-noise ratio (prepulse intensity relative to background noise). We examined this hypothesis by varying prepulse intensity and background noise intensity in order to hold three different signal-to-noise ratios constant (5, 15, and 25 dB(A) above background noise intensity). The results showed that signal-to-noise ratio proved to be a more important factor than absolute stimulus intensity in determining the degree of PPI of startle eyeblink response magnitude. Therefore, the effectiveness of a prepulse is determined by prepulse salience, not intensity, and this effectiveness is equivalent across a range of physical intensities.

Effects of prepulse intensity, duration, and bandwidth on perceived intensity of startling acoustic stimuli.

Intense abrupt stimuli can elicit a startle reflex; a weak "prepulse" 30-300 ms earlier can reduce both startle and perceived stimulus intensity. Prepulse inhibition (PPI) of startle, an operational measure of sensorimotor gating, is used to understand brain disorders characterized by gating deficits. Compared to startle, PPI of perceived stimulus intensity (PPIPSI) may provide information that is distinct, and easier to acquire and analyze. To develop this experimental measure, we examined PPIPSI under different stimulus conditions. Both PPI and PPIPSI exhibited a non-linear relationship to prepulse intensity, with prepulses 15 dB(A) above background causing maximal inhibition of both measures. A 50 ms broadband noise prepulse produced maximal PPI and PPIPSI, whereas 5 and 20 ms pure tone prepulses produced maximal PPIPSI and PPI, respectively. PPIPSI is a robust, parametrically sensitive and "low tech" measure of sensory gating that may become a valuable tool for understanding the biology of certain mental disorders.

A comparison of several methods used to quantify prepulse inhibition of eyeblink responding.

Several methods of quantifying prepulse inhibition (PPI) of eyeblink responding were compared in adult volunteers. Blink-eliciting stimuli were noise bursts at 85 or 100 dB, and prepulses were also noise bursts, at 55 or 70 dB and lead intervals of 60 or 120 ms. PPI was evaluated by comparing reactivity on prepulse and control trials within participants using the following methods: (1) difference between reactivity on prepulse and control trials; (2) reactivity on prepulse trials divided by that on control trials (proportion of control); (3) difference between reactivity on prepulse and control trials, divided by that on control trials (proportion of the difference from control); (4) range correction (maximum minus minimum reactivity, divided by the range of reactivity), across all control and prepulse trials; (5) z scores across all prepulse and control trials. Prepulses inhibited eyeblink response magnitude in all cases. Proportion of difference was the method least affected by differences in control reactivity, and is the preferred method to use when quantifying PPI, both from a practical and a neurophysiological perspective.