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PubMed2003

The relationship of age to prepulse inhibition and habituation of the acoustic startle response.

Prepulse inhibition (PPI) of the startle response reflects an early stage of information processing that is abnormal in schizophrenia and certain other specific neuropsychiatric disorders that are distinguished by the inability to inhibit redundant or relatively irrelevant sensory, cognitive, or motor information. The goal of the present study was to characterize the effect of normal aging on PPI and habituation of the startle response and to examine the hypothesis that normal aging is characterized by a global decline in inhibitory function. Ninety-seven non-psychiatric controls (age range 18-88) were tested for startle eyeblink response using electromyogram (EMG) recording. Startle magnitude decreased and startle latency increased with aging. PPI demonstrated an inverted U-shaped function with age (greatest PPI at intermediate ages) while there was no significant effect of age on startle habituation. The results do not support the theory that aging is associated with a general decline in inhibitory function and contrast with previous studies that have compared only extreme age groups and have found no effects of age on PPI.

Acoustic Stimulation↗
PubMed2000

The superior olivary complex is necessary for the full expression of the acoustic but not tactile startle response in rats.

The acoustic startle response (ASR) in rats is mediated by an oligosynaptic pathway from the cochlea via the brainstem to spinal and cranial motoneurons. The present study tested whether the superior olivary complex (SOC) plays a role in the mediation of the ASR. The SOC receives auditory information from the ventral cochlear nuclei and projects to the caudal pontine reticular nucleus (PnC), the sensorimotor interface of the ASR. Axon-sparing excitotoxic lesions of the SOC strongly reduced the ASR amplitude and slightly prolonged ASR onset and peak latencies. The integrity of PnC which is adjacent to the SOC was confirmed by testing the tactile startle response which was not affected by SOC lesions. We suggest that the SOC is necessary for a full expression of the ASR and discuss possible auditory input structures involved in the mediation of the ASR.

Acoustic Stimulation↗
PubMed2001

Startle response during smoking and 24 h after withdrawal predicts successful smoking cessation.

RATIONALE: The startle response is thought to reflect changes in attentional processes in humans. The startle response shows a number of forms of plasticity, of which prepulse inhibition (PPI) refers to the attenuation of the startle response to a strong sensory stimulus (pulse), when such a pulse is preceded by a stimulus of lower intensity (prepulse). Recent studies have shown that nicotine modulates startle and PPI of the startle reflex in humans and animals. The present study examined individual differences in cognitive benefits obtained from smoking as indexed by startle response and PPI. OBJECTIVES: We investigated, using a within-subjects design, the effects of cigarette smoking via a comparison of baseline and withdrawal measures of startle and PPI in 18 subjects wishing to quit cigarette smoking. The relapse of five of these subjects enabled a between-group comparison of these measures with the successful quitters. METHODS: Startle and PPI were measured on three separate occasions: before quitting, 24 h after quitting and 1 month after quitting. RESULTS: The presence of a high startle response amplitude while subjects were still engaged in their normal smoking patterns (baseline) and the occurrence of a significant drop of startle amplitude in withdrawal relative to baseline factors were found to be predictive of an individual's ability to quit smoking. Changes in PPI were found to reflect these changes in startle amplitude. CONCLUSIONS: The observed response patterns are discussed in terms of individual differences in commitment to quitting and self-dosing to manipulate attentional mechanisms as measured by the acoustic startle response. Furthermore, it is suggested that these specific response profiles may be predictive of the ability to quit smoking.

Adult↗
PubMed2000

Auditory startle response in trauma survivors with posttraumatic stress disorder: a prospective study.

OBJECTIVE: Previous studies have shown elevated autonomic responses to startling tones in trauma survivors with chronic posttraumatic stress disorder (PTSD). The origin of these abnormal responses is obscure. The present study attempted to clarify this issue by prospectively evaluating responses to sudden, loud tones in individuals who arrived at a hospital emergency room after psychologically traumatic events. METHOD: By using a previously established protocol, autonomic and muscular responses to the tones were evaluated at 1 week, 1 month, and 4 months after the traumatic event. Structured diagnostic interviews performed at 4 months classified subjects into groups with (N=36) and without (N=182) PTSD, which were further subdivided according to the presence or absence of major depressive disorder as follows: neither PTSD nor depression (N=166), depression alone (N=16), PTSD alone (N=21), and both PTSD and depression (N=15). RESULTS: The groups showed comparable physiological responses to the tones at 1 week posttrauma. However, at 1 and 4 months posttrauma, the subjects with PTSD showed a greater heart rate response and required more stimulus trials to reach the criteria of skin conductance and orbicularis oculi electromyogram nonresponse. These findings were not significantly influenced by comorbid depression and were not explained by the severity of the traumatic event or by the intensity of the initial symptoms. CONCLUSIONS: Differences in physiological response to startling tones develop along with PTSD in the months that follow a traumatic event. This pattern supports the theories that associate PTSD with progressive neuronal sensitization.

Accidents, Traffic↗
PubMed1997

Inbred strain differences in prepulse inhibition of the mouse startle response.

Prepulse inhibition is the phenomenon in which a weak prepulse stimulus suppresses the response to a startling stimulus. Patients with schizophrenia have impaired prepulse inhibition which is thought to reflect dysfunctional sensorimotor gating mechanisms. To investigate the potential genetic basis for differences in sensorimotor gating, the responses of 13 inbred strains of mice were evaluated using the prepulse inhibition paradigm. Ten male mice from A/J, AKR/J, BALB/cByJ, BUB/BnJ, C3H/HeJ, C57BL/6J, C57BL/10J, DBA/2J, FVB/NJ, ST/bJ, 129/J, 129/SvJ, 129/SvEvTac inbred strains were tested for acoustic prepulse inhibition of acoustic and tactile startle responses. There was a wide range of responses among the inbred strains of mice. Exact strain distributions were determined for each combination of prepulse sound level and startle stimulus. In general, mice from the 129/SvEvTac, AKR/J, 129/J, and 129/SvJ strains displayed high levels of prepulse inhibition of both the acoustic and tactile startle responses. C57BL/6J, C57BL/10J and BUB/BnJ mice showed low levels of prepulse inhibition. There was also a wide range in the amplitude of the acoustic and tactile startle responses. C57BL/10J and FVB/NJ mice displayed the greatest startle responses and DBA/2J, 129/J and 129/SvJ had the poorest startle responses. There was no correlation between the level of prepulse inhibition and the amplitude of the startle response. These findings indicate that inbred strains of mice may be a useful tool to study the genetic basis of sensorimotor gating.

Acoustic Stimulation↗
PubMed1976

The startle response in rats: effect of ethanol.

The effects of acute and chronic ethanol intake on the startle response was examined in male rats. Ethanol given IP produced a dose-dependent decrease in the amplitude of the startle response measured 30 min later. With a dose of 1 g/kg, the effect was evident at 15 min and had recovered substantially by 60 min. The effect of ethanol on the startle response was potentiated by pretreatment of the animals with pimozide, haloperidol, and p-chlorophenylalanine but not by propranolol, phenoxybenzamine, alpha-methyltyrosine, or pargyline. After 3 weeks on an ethanol-containing diet, the startle response was greater than that shown by rats on the control iso-caloric, sucrose-containing diet. After ethanol withdrawal, the startle response was further increased, with a peak about 9 to 12 hr after discontinuation of ethanol; thereafter, the response declined. This time course of heightened startle response during ethanol withdrawal corresponds to the time course of the activation of noradrenergic neurons during withdrawal. It appears that dopaminergic and serotonergic neurons are involved in the mediation of the startle response in rats.

Adrenergic alpha-Antagonists↗
PubMed2005

Neural monoaminergic mediation of the effect of St. John's wort extract on prepulse inhibition of the acoustic startle response in rats.

Prepulse inhibition (PPI) of startle response is a valuable paradigm for sensorimotor gating processes by which an organism filters sensory information. Disruption of PPI is evident in schizophrenia and Huntington's disease among other neuropsychiatric disorders characterized by sensorimotor gating deficit. In such disorders, increased brain monoamines' transmission was suggested to underlie PPI disruption. The effect of St. John's wort extract on PPI of startle response is yet to be investigated despite research findings indicating augmented levels of brain monoaminergic function after acute administration of the extract. In this study, the effect of acute oral administration of St. John's wort extract (62.5, 125, 250 and 500 mg/kg) was tested on PPI of an acoustic startle response in rats. A disruption of PPI resulted after the administration of the highest dose of the extract and therefore its effect on dopaminergic, serotonergic and noradrenergic neurotransmission was investigated in a number of rat brain areas involved in mediation of PPI response. Results demonstrated that 500 mg/kg of the extract augmented dopaminergic transmission in the thalamus together with elevating noradrenergic transmission in both brainstem and hippocampus. In addition, increased serotonin levels in brainstem, thalamus, cortex and hippocampus were evident after administration of the same dose of the extract. It was therefore concluded that St. John's wort extract (500 mg/kg) reduced PPI response possibly through enhancing monoaminergic transmission in brainstem, thalamus, cortex and/or hippocampus. Clinical investigations are therefore needed to determine whether St. John's wort extract may affect sensorimotor gating in both schizophrenia and Huntington's disease.

Acoustic Stimulation↗
PubMed2001

Influence of gender on auditory startle responses.

The auditory startle reaction is considered a brainstem reflex in response to an unexpected loud stimulus. It may be abnormal in various neurological conditions. However, the influence of gender on physiological characteristics of auditory startle responses (ASRs) in humans has to date been studied only in orbicularis oculi muscle. We investigated 54 healthy adult subjects (27 males, 27 females). ASRs were elicited by binaural high-intensity auditory stimuli which differed randomly in tonal frequency and intensity (250 Hz-90 db; 500 Hz-105 dB; 750 Hz-110 db, 1000 Hz-110 dB nHL), presented through tubal insert phones. Reflex electromyographic activity was simultaneously recorded with surface electrodes from masseter, orbicularis oculi, sternocleidomastoid, biceps brachii, abductor pollicis brevis, rectus femoris, tibialis anterior, and soleus muscles. ASR probability was significantly lower, and ASR area under the curve was significantly smaller, in men versus women. Median onset latencies did not differ significantly, but tended to be shorter in the lower extremities of men despite greater body height. Habituation, measured as a reduction in response probability with repeated stimulation, was significant in all muscles except orbicularis oculi in both men and women. Our data provide evidence for a significant influence of gender on ASR characteristics. The observed differences are likely due to gender-specific variations of central processing in the brainstem centers involved in ASR generation, and should be taken into account when testing ASRs in health and disease.

Acoustic Stimulation↗
PubMed1996

Fetal startle response observed under ultrasonography: a good predictor of a reassuring biophysical profile.

OBJECTIVE: To correlate the vibroacoustic stimulus-evoked fetal startle response observed under ultrasonography with the subsequent biophysical profile (BPP) score. METHODS: Vibroacoustic stimulation was applied under ultrasound observation to gravidas who had a nonreactive fetal heart rate in the first 10 minutes of monitoring. Fetal startle response was defined as a sudden movement of fetal extremities in the 2 seconds following stimulus. Subsequently, nonstress testing was completed and a BPP performed on all women who required vibroacoustic stimulation. The presence or absence of a fetal startle response was compared with the observed BPP score. RESULTS: Two hundred tests were performed at 35.3 +/- 3.7 weeks. After the vibroacoustic stimulation, 70% of the nonreactive tracings became reactive. Mothers perceived the fetal startle response after vibroacoustic stimulus in 93% of cases. All cases with a fetal startle response after a vibroacoustic stimulation had a subsequent BPP score of 8 or more (negative predictive value of 100%). In addition, all patients with a nonreassuring BPP score were in the group of patients with absent fetal startle response. However, the positive predictive value of an absent fetal startle response for a subsequent BPP score of 6 or less was only 10%. CONCLUSION: This preliminary study suggests that the fetal startle response predicts a BPP score equal to or greater than 8. After the availability of larger studies supporting these findings, this test could be used as a rapid antepartum test to predict fetal well-being.

Acoustic Stimulation↗
PubMed2000

Involvement of the human medial cerebellum in long-term habituation of the acoustic startle response.

Animal studies have shown an involvement of the cerebellar vermis in long-term habituation of the acoustic startle response, but not in short-term habituation. The aim of the present study was to investigate whether short-term and long-term habituation of the acoustic startle response are impaired in patients with medial cerebellar lesions. Five patients with midline cerebellar lesions due to surgery for astrocytoma and ten healthy, age- and sex-matched subjects were studied. Subjects received 40 acoustic startle stimuli each day on five successive days. Peak amplitudes of the startle response recorded at the orbicularis oculi and the sternomastoid muscles were obtained. Data were analyzed for response decrement within the training session of one day (short-term habituation) and for a decrease in the startle response across the five training days (long-term habituation). Short- and long-term habituation of the startle response recorded at the sternomastoid muscles could be achieved in controls and in cerebellar patients. However, long-term habituation of the blink component of the acoustic startle response recorded at the orbicularis oculi muscles was significantly impaired in patients with cerebellar lesions compared with control subjects, whereas short-term habituation was preserved in both groups. The present findings suggest that the medial cerebellum is involved in long-term habituation of the blink component of the startle response in humans.

Adolescent↗
PubMed2003

Neonatal lesions in the amygdala or ventral hippocampus disrupt prepulse inhibition of the acoustic startle response; implications for an animal model of neurodevelopmental disorders like schizophrenia.

Prepulse inhibition of the acoustic startle response is a behavioural tool applied to assess sensorimotor gating processes in humans and rats. Schizophrenic patients show deficits in prepulse inhibition of the acoustic startle response. The animal model of neurodevelopmental disorders such as schizophrenia, as purported in earlier reports and the present study, is based on the assumption that damage to brain structures early in life (on day 7) disrupts brain maturation of structures connected to the damaged areas, measurable by behavioural changes, whereas similar damage later in life (on day 21) does not result in these behavioural changes. Locomotor activity, the acoustic startle response and its prepulse inhibition were investigated in adult rats lesioned in the amygdala or ventral hippocampus on day 7 or 21 of life. The acoustic startle response was increased in animals lesioned in the amygdala on day 7 or 21 of life, but not in animals lesioned in the ventral hippocampus. Prepulse inhibition was impaired and locomotor activity enhanced in animals lesioned in the amygdala or ventral hippocampus on day 7, but not in animals lesioned in these structures on day 21 of life. The results on the acoustic startle response are suggestive of amygdaloid influences on modulation of the acoustic startle response. The effects of early postnatal lesions on prepulse inhibition and locomotor activity are in support of the animal model of neurodevelopmental disorders like schizophrenia.

Acoustic Stimulation↗
PubMed1999

Cholinergic modulation of the acoustic startle response in the caudal pontine reticular nucleus of the rat.

The startle response is a useful behavioural model to assess drug effects on sensorimotor information processing in the mammalian central nervous system. Prepulse inhibition of the acoustic startle response in rats is an operational measure for sensorimotor gating mechanisms which may be necessary for attention and response selection. The caudal pontine reticular nucleus is a key element of the pathway that mediates the acoustic startle response and receives an inhibitory cholinergic projection that might be important for prepulse inhibition. The present study tested whether prepulse inhibition of acoustic startle is modulated by microinfusions of the muscarinic/nicotinic acetylcholine receptor agonist carbachol and of the muscarinic acetylcholine receptor antagonist scopolamine. Carbachol (0-40 nmol/0.5 microl) dose dependently attenuated startle and enhanced prepulse inhibition. Scopolamine (0-40 nmol/0.5 microl) dose-dependently enhanced startle and reduced prepulse inhibition at a dose of 10 nmol. Scopolamine (40 nmol) also increased the spontaneous motor activity of the rats. These findings lend support to the hypothesis that muscarinic acetylcholine receptors in the caudal pontine reticular nucleus inhibit the acoustic startle response and are involved in the mediation of prepulse inhibition of startle.

Acoustic Stimulation↗
PubMed1999

Decrease in occurrence of fast startle responses after selective Mauthner cell ablation in goldfish (Carassius auratus).

A single action potential in one of a pair of reticulospinal neurons, the Mauthner cells, precedes a short-latency electromyographic response of the trunk and tail musculature on the opposite side of the body and a fast startle response in goldfish. It has been postulated that not only the Mauthner cell, but also an array of neurons can trigger or participate in fast startle responses (Eaton et al. 1991). We have selectively ablated the Mauthner cells in goldfish to study how neurons of the brainstem fast startle response network interact. The probability of eliciting a fast startle response was significantly less in fish with double Mauthner cell ablations, as compared to the responsiveness of control fish. The finding that there is a significant decrease in the occurrence of fast startle responses in animals with no Mauthner cells, implies that the Mauthner cell may play a role in triggering the involvement of the other network elements in fast startle responses. We hypothesize that Mauthner cell activation may be important in bringing those reticulospinal neurons that are "primed" by the behavioral context to threshold and provides the basis for studies focused on the interactive nature of the brainstem startle response network.

Animals↗
PubMed1997

Serotonin-1A antagonists attenuate the effects of nicotine withdrawal on the auditory startle response.

Withdrawal from the chronic administration of nicotine has previously been shown to lead to an enhanced auditory startle response in rats. In order to explore the neuropharmacology and neurophysiology underlying this phenomenon, we examined the effects of various 5-hydroxytryptamine (5-HT)-1A antagonists and agonists on the nicotine-withdrawal-enhanced auditory startle response in male rats. Animals were treated with nicotine (6 mg/kg/day nicotine base, via subcutaneously implanted osmotic minipumps) for 12 days. After 12 days the pumps were removed and the animals allowed to undergo spontaneous withdrawal for several days. In agreement with previous results, nicotine withdrawal led to a significant elevation of the auditory startle response. Pretreatment with the 5-HT-1A agonists (+)8-OH-DPAT (0.001-0.1 mg/kg) and LY274600 (0.3-3.0 mg/kg) either had no affect or exacerbated the nicotine-withdrawal-enhanced startle response. Pretreatment with the 5-HT-1A antagonists NAN-190 (1-3 mg/kg), LY206130 (1-10 mg/kg), or WAY-100635 (0.1-1.0 mg/kg) blocked the increase in the startle response caused by nicotine withdrawal at doses that had no effect on baseline startle responses. These data indicate that 5-HT-1A receptors play a role in the neurophysiology of nicotine withdrawal. In addition, 5-HT-1A antagonists may be able to relieve some nicotine withdrawal symptoms in man and may represent a novel pharmacotherapy for smoking cessation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2005

Baseline and modulated acoustic startle responses in adolescent girls with posttraumatic stress disorder.

OBJECTIVE: To assess baseline and modulated acoustic startle responses in adolescent girls with posttraumatic stress disorder (PTSD). METHOD: Twenty-eight adolescent girls with PTSD and 23 healthy control girls were recruited for participation in the study. Acoustic stimuli were bursts of white noise of 104 dB presented biaurally through headphones. Baseline startle responses as well as prepulse inhibition, a 1,000-Hz prestimulation tone presented 120 milliseconds before the startle stimulus for 30 milliseconds, and prepulse facilitation, a 1000-Hz prestimulation tone presented continuously for 2, 000 milliseconds before the startle stimulus, were compared in these two groups of girls. RESULTS: At baseline and under neutral testing conditions, the magnitude of the startle response (eye blink) did not differ significantly between girls with PTSD and healthy control girls. There were no significant differences in the degree of prepulse inhibition or facilitation between the two groups of girls. CONCLUSIONS: Unlike combat veterans with PTSD, adolescent girls with PTSD who report exaggerated startle may not have exaggerated baseline acoustic startle responses in the laboratory. Further research should explore whether girls with PTSD demonstrate altered startle responses under stress and/or evidence of other types of psychophysiological abnormalities.

Acoustic Stimulation↗
PubMed1998

Involvement of the human cerebellum during habituation of the acoustic startle response: a PET study.

The present study investigated the involvement of the human cerebellum in the habituation of the acoustic startle response using PET. The startle response was elicited in seven young, healthy subjects by a tone presented via headphones. Startle responses were recorded from the right sternocleidomastoid muscle. Regional cerebral blood flow (rCBF) was assessed in nine scans and one startle stimulus was applied during each scan. The reduction of size of the sternocleidomastoid muscle response was correlated with changes in rCBF during the ongoing process of startle response habituation. A significant decrease of rCBF was found in the medial cerebellum. These data are consistent with an involvement of the medial parts of the human cerebellum in non-associative learning as proposed by previous animal studies.

Acoustic Stimulation↗
PubMed1993

Glutamate antagonists in the reticular formation reduce the acoustic startle response.

A previous study has shown that the acoustic responsiveness of reticulospinal neurones in the caudal pontine reticular nucleus (PnC) is reduced by glutamate antagonists. It was postulated that the acoustic startle response is mediated by glutamate receptors on PnC-neurones. In the present study, we tested this hypothesis by local microinjections of different glutamate antagonists into the PnC of unrestrained awake rats. In order to differentiate the drug effects on the head and body startle responses, we measured the head startle response electromyographically, and the body startle response in a ballistic chamber. Both the AMPA/kainate and the NMDA receptor antagonists reduced both components of the startle response dose-dependently. We conclude that both subtypes of ionotropic glutamate receptors in the PnC are relevant for the acoustic startle response in rats.

2-Amino-5-phosphonovalerate↗
PubMed1993

Acoustic startle response and habituation in freezing and nonfreezing rats.

Rats can be divided according to their responses to startle-eliciting stimuli into 2 groups with different emotional states. About half of the 54 female Sprague-Dawley rats showed long-lasting freezing behavior after 1-8 stimuli (10 kHz, 110 dB spl). In freezing rats the startle amplitude was higher than in nonfreezing rats, even on the very first startle response. This finding demonstrates that the anxiety state of these animals before the first startle-eliciting stimulus, and not just the aversiveness of the stimulus, contributes to freezing behavior. In addition, in freezing rats there was no influence of spontaneous motor activity or of adaptation time on startle amplitude. Only in nonfreezing rats were high motor activities correlated with lowered startle amplitudes, and only in these rats did the course of startle habituation depend on adaptation time.

Animals↗