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PubMed2005

Startle response in inpatients with borderline personality disorder vs. healthy controls.

Startle response is found to be enhanced in conditions that are accompanied by intense emotions, high levels of anxiety in particular. We assessed the autonomous and behavioral component of the startle reflex in a sample of 28 unmedicated inpatients with borderline personality disorder (BPD) compared to 28 controls. Amplitudes of electrodermal and startle response as well as habituation were measured in response to 15 bursts of white noise (100-db, 40-ms). We assessed prepulse inhibition to study gating capacities in BPD, with each prepulse (70-db, 30-msec) delivered 100 ms before the startling tone. In contrast to our hypothesis, our study revealed neither enhanced amplitudes of autonomic and electromyographic startle responses nor differences in habituation compared to healthy controls. In addition, no deficit in prepulse inhibition was found in BPD. In summary, our data indicate normal response to unconditioned threatening stimuli as well as normal gating capacities in BPD.

Acoustic Stimulation↗

PubMed1999

Novel antipsychotic-like effects on prepulse inhibition of startle produced by a neurotensin agonist.

Agonists of the neuropeptide neurotensin have been proposed as potential novel antipsychotics based on their ability to modulate neurotransmission in brain regions associated with schizophrenia. To test this hypothesis, we examined the effects of a neurotensin mimetic with improved metabolic stability in an animal model with strong predictive validity for antipsychotic activity. Subcutaneous injections of PD149163, a reduced amide neurotensin(8-13) mimetic, significantly antagonized the reduction of prepulse inhibition (PPI) of the rat startle reflex produced by amphetamine and by the phencyclidine analog dizocilpine. PD149163 had no significant effect on baseline PPI or on baseline startle amplitude and did not antagonize the reduction of PPI produced by the direct dopamine agonist apomorphine. These findings suggest that PD149163 has novel antipsychotic-like properties that are distinct from known members of both the "typical" and "atypical" families of antipsychotics.

Adrenergic Agents↗

PubMed1997

Fear-potentiated startle in two strains of inbred mice.

The fear-potentiated startle paradigm has been used with great success to examine conditioned fear in both rats and humans. The purpose of this study was to examine fear-potentiated startle in inbred mice. One-month-old C57BL/6J (C57) and DBA/2J (DBA) mice were given tone + foot shock training trials. The amplitude of the acoustic startle reflex was measured in the presence and absence of the tone both before and after training. Both strains showed fear-potentiated startle after training as evidenced by larger startle amplitudes in the presence of the tone than in its absence. However, the magnitude of fear-potentiated startle was greater in DBA mice than in C57 mice. These results not only demonstrate fear-potentiated startle in mice for the first time but also suggest that fear-potentiated startle can be influenced by characteristics of the mouse strain.

Acoustic Stimulation↗

PubMed1997

Reduced prepulse inhibition after electrolytic lesions of nucleus accumbens subregions in the rat.

A variety of neurochemical and anatomical studies have shown that the ventral striatal nucleus accumbens (NAcc) can be divided into a predominantly medial 'shell' and a predominantly lateral 'core'. These accumbens subdivisions are innervated by different cortical regions and project to different anatomical targets. Additionally, recent behavioral observations suggest functional differences between the accumbens shell and core. In order to further examine core and shell function, we measured prepulse inhibition (PPI) of the acoustic startle reflex after electrolytic lesions aimed at the central NAcc, the NAcc shell, the NAcc core, and the adjacent anteroventrolateral striatum. Acoustic startle is the contraction of whole-body musculature in response to a sudden, loud auditory stimulus, and PPI is the inhibition of acoustic startle by a weak auditory 'prepulse' administered 30-500 ms prior to the startling stimulus. Previous work has shown that PPI is regulated by the NAcc, and recent observations suggest that PPI is regulated by different neurochemical interactions in the core and shell. PPI was significantly reduced by electrolytic lesions of the central NAcc, as well as by lesions that predominantly damaged either the NAcc shell or the core. Lesions of the anteroventrolateral striatum and lateral edge of the NAcc core did not significantly alter PPI. These findings suggest that, despite neurochemical differences between the two subregions, PPI is regulated by both the NAcc shell and core.

Acoustic Stimulation↗

PubMed1975

Developmental and behavioral changes in the rat during chronic exposure to lead.

Young male and female Sprague-Dawley rats were given drinking water containing 5 or 50 ppm Pb for 40 days prior to mating. Pregnant females were continued on these regimens throughout gestation and lactation. After weaning the offspring were similarly exposed through adulthood. Reflex development, body weights, and locomotor activity were measured in the offspring. Significant delays were noted in the development of the righting reflex at 5 and 50 ppm and in eye opening at 50 ppm. No difference was observed in development of the startle reflex at either dose. Mean body weights of treatment groups during this developmental period were not significantly different from controls. Locomotor activity was measured in adult males utilizing a residential maze. Both levels of lead produced a significant reduction in locomotor activity. When groups were treated with d-amphetamine (4.0 mg/kg subcutaneous), lead treatment caused a dose-related diminution in the amphetamine-induced hyperactivity. These results indicate that rats exposed to low levels of lead from conception until adulthood show a delay in nervous system development. As adults, these animals exhibit hypoactivity and decreased responsiveness to amphetamine.

Aging↗

PubMed1995

Circadian modulation in the rat acoustic startle circuit.

The acoustic startle reflex (ASR) in rats exhibits robust circadian modulation, with ASR amplitudes greater during subjective night. To identify the location of this modulation, startle reactions were evoked either acoustically or electrically via electrodes implanted in the primary ASR circuit. Startle amplitudes were compared at different times in the circadian cycle. In constant environmental conditions, startle amplitudes were greater in subjective night for acoustically evoked and for electrically evoked reactions from the ventral lateral lemniscus and medial longitudinal fasciculus. The results show that at least 1 site of circadian modulation must occur at some point in the circuit after the last brainstem synapse in the caudal pontine reticular formation, at the level of spinal interneurons or motoneurons or at the neuromuscular junction.

Animals↗

PubMed1998

Effect of darkness on acoustic startle in Vietnam veterans with PTSD.

OBJECTIVE: Exaggerated startle is a symptom of posttraumatic stress disorder (PTSD), but empirical studies have not consistently documented elevated baseline startle in PTSD. The authors proposed in a previous study that Vietnam veterans with PTSD exhibit exaggerated startle only under stressful conditions. They reported that darkness facilitated startle in humans, suggesting that the startle reflex is sensitive to the aversive nature of darkness. In the present study they tested the hypothesis that the magnitude of facilitation of startle by darkness would be greater in Vietnam veterans with PTSD than in comparison groups of subjects without PTSD. Prepulse inhibition was also investigated. METHOD: The magnitude of startle and prepulse inhibition were assessed in alternating periods of darkness and light in 19 nonmedicated Vietnam veterans with PTSD, 13 Vietnam veterans without PTSD, and 20 civilians without PTSD. RESULTS: The overall startle level was higher in the veterans with PTSD than in either of the two groups of subjects without PTSD. Startle was facilitated by darkness, and the magnitude of this facilitation was greater in the veterans with PTSD than in the civilians without PTSD, but it was not greater in the veterans without PTSD. Prepulse inhibition was not affected by darkness and did not significantly differ among groups. CONCLUSIONS: Contrary to the hypothesis, elevated sensitivity to darkness was specific to individuals with combat experience, not to individuals with PTSD, perhaps because veterans had become aversively conditioned to darkness during their combat experiences. The more general increase in startle reactivity in the veterans with PTSD is consistent with clinical observations and descriptions of symptoms in DSM-IV.

Acoustic Stimulation↗

PubMed1999

Effects of bilateral electrical stimulation of the ventral pallidum on acoustic startle.

The ventral pallidum (VP) is believed to occupy a critical position between the limbic and the motor systems, for transferring motive information into motor commands. To estimate the time course of signaling from the VP to motor outputs, in the present study we examined the effects of bilateral electrical stimulation of the VP on the acoustic startle reflex in awake rats. When the interstimulus interval (ISI) between VP stimulation and acoustic stimulation was shorter than 5 ms, VP stimulation potentiated acoustic startle. When the ISI was longer than 5 ms, VP stimulation inhibited acoustic startle over a large range of ISIs with the maximum inhibition at ISIs between 15 and 25 ms. In contrast, bilateral electrical stimulation of the amygdala did not have a significant inhibitory effect on acoustic startle, but strongly augmented acoustic startle at shorter ISIs (0-10 ms). Compared to unilateral electrical stimulation of the inferior colliculus (IC), bilateral stimulation of the VP gave rise to a rightward shift of the ISI curve, indicating that the neural pathways conveying the inhibitory influence from the VP to the acoustic startle circuit are longer than those from the IC.

Acoustic Stimulation↗

PubMed1998

A sensory-enhanced context facilitates learning and multiple measures of unconditioned stimulus processing in the preweanling rat.

This study tested the hypothesis that increased processing or efficacy of the unconditioned stimulus (US) contributes to the facilitation of trace conditioning that occurs when preweanling rats are conditioned in a novel sensory-rich context. Experiment 1 extended previous findings (D. L. McKinzie & N. E. Spear, 1995) of facilitated acoustic trace conditioning in the 17-day-old rat in a sensory-enhanced versus a home odor context. In the enhanced or more familiar context, Experiment 2 tested rats of this age for degree of spontaneous locomotor activity and ultrasonic vocalizations, activity and ultrasounding in response to shock, and the acoustic startle reflex. The enhanced context resulted in a greater overall activity response to shock, increased ultrasounding to discrete shocks, and a sensitized latency to startle. The results suggest that enhanced US processing in a sensory-rich context is a likely contributor to its facilitative effect on infant learning.

Animals↗

PubMed2005

The neuropsychology of fear learning and fear regulation.

In the current review article it is suggested that fear is a central emotional state that can be activated by external threat cues. The subcortical defensive system cannot only be activated by intrinsically aversive events but shows also strong plasticity enabling previously innocuous stimuli to get access to the fear system after they were paired with painful outcomes. On the other hand, aversive conditioning does not only result in the acquisition of a defensive disposition, the organism also learns on a pure cognitive level that one stimulus predicts the occurrence of another stimulus. It is suggested here that potentiation of the acoustic startle reflex is a rather specific measure for fear acquisition, while skin conductance discrimination indexes contingency learning. It is shown that the acquisition of fear-potentiated startle does not require cortical processing of the conditioned stimulus. Moreover, data indicate that conditioned startle potentiation is abolished in patients with unilateral lesions of the amygdala. Finally, conditioned startle potentiation can be obtained without contingency awareness, which on the other hand is necessary for skin conductance conditioning to occur. It is suggested that the learning of stimulus relations is mediated by the hippocampus and that conditioned startle potentiation is also mediated by the hippocampus in trace conditioning.

Animals↗

PubMed1977

Plasticity of the acoustic startle response in the acutely decerebrate rat.

Plasticity of the acoustic startle reflex was measured in rats in which a complete transection between the forebrain and midbrain was made. During a period from 60 to 100 min after surgery, startle amplitude in the transected rats was relatively stable and comparable with that of the controls (which had been anesthetized with halothane and placed in a stereotaxic instrument). During this period the transection did not alter the temporal recovery process (with intervals of 2, 4, 8, or 16 sec) or auditory prepulse inhibition (with intervals of 25, 50, 100, 500, or 1,000 msec) or the normal reduction in startle caused by high levels of background noise. The transection did prevent the normal increase in startle caused by moderate levels of background noise and eliminated within-session habituation. The effect on habituation was particularly convincing since the curves of the transected and nontransected rats actually crossed. The results are discussed in terms of how the transection procedure can be used to evaluate various hypotheses about underlying mechanisms of startle plasticity.

Acoustic Stimulation↗

PubMed1999

Fear-potentiated startle conditioning to explicit and contextual cues in Gulf War veterans with posttraumatic stress disorder.

Aversive conditioning to explicit and contextual cues was examined in Gulf War veterans with and without posttraumatic stress disorder (PTSD) by use of the startle reflex methodology. Veterans participated in a differential aversive conditioning experiment consisting of 2 sessions separated by 4 or 5 days. Each session comprised two startle habituation periods, a preconditioning phase, a conditioning phase, and a postconditioning extinction test. In contrast to the non-PTSD group, the PTSD group showed a lack of differential startle response in the presence of a conditioned stimulus with or without an unconditioned stimulus in Session 1 and an increase in the baseline startle response during Session 2. The PTSD group also exhibited normal differential conditioning following reconditioning in Session 2. These data suggest that individuals with PTSD tend to generalize fear across stimuli and are sensitized by stress.

Adult↗

PubMed1986

Visual function measured by reflex modification in rats with inherited retinal dystrophy.

Developmental changes in visual function were studied in the Royal College of Surgeons (RCS) rat with inherited retinal degeneration by examining the inhibition of acoustic startle reflexes by visual prestimuli. Compared with a congenic strain of nondystrophic rat, the RCS rats showed an increase in the interstimulus interval between the inhibitory prestimulus and the eliciting stimulus that produced maximal inhibition, a result suggesting a decrease in the speed of processing. The amount of inhibition also decreased over time, which suggests a progressive loss of visual function. Simultaneous presentation of auditory and visual prestimuli was used to demonstrate that the changes in inhibition were related to alterations in visual function and that auditory function was not impaired in these rats. The results show that reflex modification is a suitable test for evaluating visual dysfunction in rats.

Acoustic Stimulation↗

PubMed2003

Anxiolytic effects of a novel group II metabotropic glutamate receptor agonist (LY354740) in the fear-potentiated startle paradigm in humans.

RATIONALE: LY354740, a structural analogue of glutamate that shows specificity at the mGluR2/3 receptor, has anxiolytic effects in animal models. OBJECTIVE: This study investigated the anxiolytic effects of LY354740 in humans using the fear-potentiated startle reflex methodology. METHODS: Subjects were given either placebo (n=16), 20 mg LY354740 (n=15), or 200 mg LY354740 (n=13). The fear-potentiated startle tests examined startle potentiation to shock anticipation and to darkness. RESULTS: Consistent with previous results, startle was increased by threat of shock and by darkness. LY354740 did not affect baseline startle. Correspondingly, subjects did not report LY354740 to be sedative. LY354740 significantly reduced the increase in startle magnitude during shock anticipation, but not during darkness. Subjective reports of state anxiety and negative affectivity during the fear-potentiated startle tests were also reduced in a dose-dependent manner by LY354740. CONCLUSIONS: These results suggest that LY354740 has an anxiolytic profile in humans without being sedative.

Administration, Oral↗

PubMed2003

[Neurophysiology of parkinsonian syndromes].

Neurophysiological investigations may contribute to establish the diagnosis of different parkinsonian syndromes such as multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, which are often suspected in case of atypical parkinsonian syndrome. They provide a means of objective analysis of certain symptoms (myoclonus for example) and identify the pathophysiological processes underlying these parkinsonian syndromes. This article reviews especially the following electrophysiological tests: autonomic nervous system analysis (sympathetic sudomotor skin response, R-R interval variation, electromyography of the external anal sphincter), surface electromyography and movement recording to investigate myoclonus, somatosensory and motor evoked potentials, brainstem reflexes (mainly the blink reflex), startle reaction, monosynaptic and long latency reflexes and finally the premotor potentials (contingent negative variation, Bereitschaftspotential) and movement-related desynchronization).

Anal Canal↗

PubMed1999

Effects of bromocriptine and haloperidol on prepulse inhibition: comparison of the acoustic startle eyeblink response and the N1/P2 auditory-evoked response in man.

Experiments with animals have shown that D2 dopamine receptors are involved in regulating prepulse inhibition (PPI) of the acoustic startle reflex (suppression of the reflex response evoked by a loud sound by prior presentation of a low-intensity stimulus). Recently we found that PPI of the human eyeblink startle response could be suppressed by a D2 receptor agonist, bromocriptine, and that this suppression could be reversed by a D2 receptor-blocking neuroleptic, haloperidol. The present work attempted to replicate this finding and to extend it to PPI of the N1/P2 component of the auditory-evoked potential. Eleven healthy males (18-30 years) participated in four sessions in which they received oral doses of placebo, bromocriptine 1.25 mg, haloperidol 3mg and combined treatment with bromocriptine 1.25 mg + haloperidol 3 mg, according to a balanced double-blind protocol. Thirty-minute simultaneous recordings of the electromyographic (EMG) responses of the orbicularis oculi muscle of the right eye and the vertex auditory-evoked potentials took place 120 min after ingestion of haloperidol and/or 90 min after ingestion of bromocriptine. Sound stimuli (1-kHz) were presented in 60 trials separated by variable intervals (mean 25 sec): (i) 40 msec 115 dB ('pulse alone': 20 trials); (ii) 40 msec 85 dB (20 trials); (iii) 40 msec 85 dB, followed after 120 msec by 40 msec 115 dB ('prepulse/ pulse': 20 trials). The amplitudes of the EMG and N1/P2 responses were not altered significantly by any of the treatments. Bromocriptine attenuated PPI of the EMG response significantly, this attenuation being absent following combined haloperidol/bromocriptine treatment. Neither bromocriptine nor haloperidol significantly altered PPI of the N1/P2 complex. Bromocriptine suppressed and haloperidol elevated serum prolactin levels, these changes being absent when the two drugs were given in combination. The results suggest that different mechanisms may be involved in regulating PPI of the eyeblink and the N1/P2 component of the auditory-evoked potential, and that D2 receptors may be involved in the former case, but not the latter.

Acoustic Stimulation↗

PubMed1996

Baseline startle amplitude and prepulse inhibition in Vietnam veterans with posttraumatic stress disorder.

Although an exaggerated startle response is a symptom of posttraumatic stress disorder (PTSD), empirical support for elevated baseline startle in PTSD has been weak. The present study investigated the eyeblink component of the acoustic startle reflex and prepulse inhibition (PPI) in 21 unmedicated Vietnam veterans with PTSD and in 17 civilian and 10 combat veteran comparison subjects. Patients with PTSD exhibited normal acoustic startle amplitude, but showed a significant reduction in PPI relative to the civilian subjects. There was only a trend toward a reduction in PPI in the PTSD group compared with the combat control group. The study does not support the hypothesis of exaggerated baseline startle in Vietnam veterans with PTSD but suggests abnormal startle modulation by a prepulse (i.e., PPI). Discrepancies between studies concerning the amplitude of startle in PTSD are discussed.

Acoustic Stimulation↗

PubMed2004

The Impact of Event Scale--Revised: evaluation of the subscales and correlations to psychophysiological startle response patterns in survivors of a life-threatening cardiac event: an analysis of 129 patients with an implanted cardioverter defibrillator.

BACKGROUND: The aim of the present study was to examine the reliability and validity of the Impact of Event Scale-Revised (IES-R) with special emphasis on the evaluation of the hyperarousal subscale against a standardized psychophysiological measurement. METHODS: A total of 129 survivors of a life-threatening cardiac event underwent a psychodiagnostic evaluation and a psychophysiological acoustic startle reflex (ASR) paradigm. The ASR assessed the magnitude and habituation of electromyogram (EMG) and skin conductance responses (SCR) in response to the delivery of 15 acoustic startle trials. Pearson correlation and factor analysis was used to measure reliability and construct validity. The hyperarousal subscale was validated against the ASR in terms of sensitivity and specificity mainly using receiver operating characteristic (ROC) curve analysis. RESULTS: A high reliability was found for the intrusion and avoidance subscale (alpha>0.8); however, the hyperarousal subscale showed a weaker reliability (alpha=0.66). No avoidance item, one intrusion item but four hyperarousal items revealed higher correlations to another than its assigned subscale. The hyperarousal subscale was not able to discriminate sufficiently between patients with and without exaggerated startle reactions as indicated by ROC curves running near the diagonal line. LIMITATIONS: The scores in all three subscales are lower compared to subjects traumatized by non-cardiac events. CONCLUSIONS: Reliability and construct validity for the intrusion and avoidance subscale proved to be high but was only sufficient for the hyperarousal subscale. Moreover, the criterion validity of the hyperarousal subscale regarding psychophysiological measurements is arguable and indicates further investigations in this area.

Acoustic Stimulation↗