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Evoked fetal startle response: a possible intrauterine neurological examination.

The fetal startle reflex was studied in an attempt to provide an objective and quantitative estimate of the fetal neurological condition. This reflex is a normal response to a combined sound-vibratory stimulus in the healthy infant born after 30 weeks of gestation. It consists of a generalized paroxysmal motion that involves the whole body. Thirty women with uncomplicated pregnancies, who subsequently delivered healthy infants, were studied at term. Fetal movements were monitored by means of a real-time scanner. Placement of the transducer was such that it allowed for visualization of the long axis of the fetal forearm. A 3-second stimulus was delivered on the maternal abdomen over the fetal head with use of an artificial larynx. This device generates a mixed sound-vibratory output of 100 dB and 85 Hz. Sufficient visualization of the plane of forearm motion was possible 68% of the time, thus allowing for measurement of the duration of this motion. The results indicate that the mean duration of forearm motion in response to a 3-second sound-vibratory stimulus is 8.2 +/- 2.3 seconds (+/- SEM). Since an immediate forearm motion was detected each time that a stimulus was applied, we conclude that the startle reflex does indeed exist in the fetus. This simple means of assessing the neurological state of the fetus may provide a way to evaluate fetal tone as it applies to antenatal fetal assessment.

Acoustic Stimulation↗

P300 from inspiratory occlusion reflects orienting but not startle.

Sudden onset inspiratory occlusion stimuli elicit large amplitude P300 components and also startle blinks. The primary purpose of this study was to assess the influence of the startle reflex on the respiratory related P300. A secondary purpose was to assess changes in P300 scalp topography as a function of stimulus familiarity. Young adults (n=12) were exposed to 200 inspiratory occlusion stimuli, and EEG was recorded from 29 A1/A2 referenced sites. Data from the occlusions were divided into four consecutive blocks of 50 trials to assess blink and P300 habituation effects. Results showed that 40% of the occlusion stimuli elicited a blink response, and that blink amplitude showed significant habituation across the experimental session. Change in P300 amplitude across the experimental session varied according to scalp site. At central and parietal locations, P300 amplitude showed an initial decrease but then remained stable. Frontally, P300 amplitude decreased over each of the four trial blocks. P300 scalp topography showed a classic centro-parietal maximum, however, a more frontally orientated scalp focus was seen for the first trial block. P300 was not significantly different when derived from averages of responses containing and not containing blinks. These data indicate that the previously studied centro-parietal P300 is not related to a startle reflex. However, when occlusions are first presented, a scalp topography similar to that previously noted for novel stimuli is observed.

Adolescent↗

Mauthner neuron field potential in newly hatched larvae of the zebra fish.

1. Extracellular unit recording was done in the brain and spinal cord of unanesthesized zebra fish larvae embedded in a drop of gelatin under a compound microscope. Startle responses were elicited either by vibrating a stylus against the ear vesicle, or by direct electrical stimulation of the spinal cord. 2. As in adult fish, the Mauthner neurons produced a prominent negative potential (0.5-1 mV) which occurred at the beginning of the startle reflex. The axonal conduction velocity was 1.7-3.7 m/s. 3. With vibratory stimulation, the startle reflex was elicited most reliably at rates of 1/min or less, though the Mauthner cells would follow stimulation rates of 1/s when the spinal cord was stimulated electrically. At this rate there was considerable fatigue of the spike itself, which became smaller in amplitude and longer in duration. 4. The auditory system functions during vibratory stimulation of the ear vesicle, and probably activates the Mauthner cells, though it was not concluded that this was an exclusive excitatory pathway during these experiments. Lateral line or purely tactile receptors might also be involved. The latency of the Mauthner spike varied inversely (range, 6-17.5 ms) with the intensity of the vibratory stimulus. Muscle contractions began 2 ms after the Mauthner spike. 5. We recorded several forms of startle behavior, including a single tail flip or a tail flip followed by regular or irregular tail movements. The Mauthner neuron almost always fired at the beginning of the response, but it never fired again during subsequent movements. This supports an earlier contention that the Mauthner cell initiates the tail flip but is not involved in iterative swimming behavior.

Acoustic Stimulation↗

Oxytocin modulates psychotomimetic-induced deficits in sensorimotor gating.

Oxytocin plays an important role in the regulation of normal cognitive functions and behaviors, which are disturbed in schizophrenia. Several studies suggest that oxytocinergic function is abnormal in schizophrenia patients. Thus, oxytocin may be involved in the pathophysiology associated with this disorder. This study investigated the regulatory effects of oxytocin on deficits in prepulse inhibition (PPI) associated with schizophrenia. Prepulse inhibition (PPI) is an operational measure of sensorimotor gating which can be measured across many species. PPI is the normal suppression of the startle reflex when the intense startling stimulus ("pulse") is immediately preceded by a weaker stimulus ("prepulse"). Subcutaneously administered oxytocin (0.04-1.0 mg/kg) dose-dependently restored PPI that had been reduced in rats by dizocilpine, a non-competitive NMDA antagonist, and by amphetamine, an indirect dopamine agonist. Oxytocin did not produce a significant effect on baseline PPI or PPI decreased by the direct dopamine agonist, apomorphine. The underlying startle response amplitude was also not significantly altered by oxytocin. These results suggest that oxytocin may play an important role in the modulation of dopaminergic and glutamatergic regulation of PPI, and that it may act as a novel endogenous antipsychotic.

Amphetamine↗

Impaired sensorimotor gating in schizophrenia with deficit and with nondeficit syndrome.

QUESTIONS UNDER STUDY: Prepulse inhibition (PPI) is the normal suppression of the startle reflex when the intense startling stimulus is preceded by a barely detectable prepulse. PPI has been proposed to reflect a measure of sensorimotor gating or filtering. Deficits in PPI has been found in schizophrenia in various prepulse conditions. The aim of this study was to investigate whether deficits in particular prepulse conditions relate to psychopathological syndromes. METHODS: Schizophrenia was subgrouped into patients with deficit and with nondeficit syndrome using the schedule of Kirkpatrick. Schizophrenia with deficit syndrome (N = 46), schizophrenia with nondeficit syndrome (N = 21), and controls (N = 44) were compared in an acoustic startle paradigm assessing PPI (30, 60, 120, 240 and 2000 ms interstimulus intervals). A mixed ANOVA was used to analyse the PPI-data. RESULTS: Schizophrenia with deficit syndrome showed a PPI-deficit in the 60 ms prepulse condition and a reduced facilitation in the 2000 ms prepulse condition, whereas PPI in patients with nondeficit syndrome was impaired in the 240 ms prepulse condition. CONCLUSIONS: The different patterns of PPI in deficit and nondeficit patients appear to relate to the heterogeneity of schizophrenia. Thus, this study may explain the various findings in previous PPI studies in the field of schizophrenia.

Adult↗

Acute exposure to methyl or ethyl alcohol alters auditory function in the rat.

Effects of alcohol on audition were studied in the rat by examining the modification of acoustic startle reflexes by pure tone pulses and by gaps in white noise. Systematic inhibition of the startle reflex by variation in pulse intensity provides an objective measure of loudness perception, while variation in gap duration assesses temporal acuity. Groups of rats (n = 8) received four injections of 0.0, 0.25, 1.00, and 2.00 g/kg of either methyl or ethyl alcohol in increasing order at 1-hr intervals. One-half hour after the administration of each dose, loudness perception or temporal acuity was measured. Blood alcohol levels (mM) for the two alcohols obtained in control animals were equivalent following the final dose. Alcohol produced a dose-dependent reduction in baseline startle amplitude that was greater during exposure to ethanol than during methanol. Loudness functions associated with pulse intensity were not diminished by alcohol; however, inhibition produced by a gap in noise was reduced following the highest dose of either alcohol. These data are consistent both with behavioral studies that have suggested that alcohol does not affect loudness perception, and with electrophysiological experiments which indicate that alcohol disrupts temporal relationships along the primary auditory pathway.

Acoustic Stimulation↗

Mescaline: excitatory effects on acoustic startle are blocked by serotonin2 antagonists.

The ability of serotonin2 (5-HT2) antagonists to block the excitatory effects of mescaline on the acoustic startle reflex were analyzed. Mescaline (20 mg/kg) caused a consistent increase in the amplitude of the acoustic startle reflex. This effect was blocked in a dose-related fashion by the 5-HT2 antagonist ritanserin (ED50 dose = 0.25 mg/kg IP). In contrast, even a high dose of ritanserin (2.0 mg/kg) did not block the excitatory effects of amphetamine on startle. Other 5-HT2 antagonists (ketanserin, cinanserin, LY 53857) also blocked mescaline's effect, whereas the 5-HT1 antagonist pindolol (5 mg/kg) did not. These results support the hypothesis that the behavioral effects of hallucinogens are mediated by agonist actions at 5-HT2 receptors.

Animals↗

[The effects of neonatal saline injections on behaviours in DBA/2 male mice].

DBA/2 male mice were exposed to the injections of the saline (0.01 ml/g i.p.) on 1-th, 3-th, 5-th, 7-th, 9-th days after birth. Intact males were used as a control group. Adult saline-treated males displayed the increased number of crossed squares, entries in the centre and time spent in the centre during the open "field" test in comparison with intact animals. The time spent in the light compartment of the light-dark box was decreased in saline treated mice compared with intact animals. During the test of acoustic startle response the magnitude of startle reflex and prepulse inhibition didn't change the startle reflex. Saline administration in males did not affect corticosterone basal level. Sexual motivation was revealed to decrease in saline treated males. These data suggest that neonatal administration of saline induced a stable behavioral syndrome in adult DBA/2 male mice: hyperactivity, a decrease of open space fear and simultaneously an increase of some indices of anxiety.

Animals↗

Symptom correlates of prepulse inhibition deficits in male schizophrenic patients.

OBJECTIVE: Information processing, inhibitory, and gating deficits in human and animal model studies of schizophrenia are demonstrated by using prepulse inhibition of the startle reflex. Prepulse inhibition deficits in schizophrenic patients correlate with core cognitive symptoms, such as thought disorder and distractibility, but their relationship to positive and negative symptoms of schizophrenia is less clear. METHOD: Fifty-one male schizophrenic patients and 26 male normal comparison subjects were tested for prepulse inhibition of the eyeblink component of the startle reflex measured by electromyogram recording. Startling stimuli (118 dB) were presented alone (pulse only) or were preceded 60 msec by discrete prepulse stimuli of 2, 4, 8, or 16 dB above the background 70-dB noise level. In addition, patients were assessed for demographic variables, generalized symptoms (Brief Psychiatric Rating Scale), and positive and negative symptoms. RESULTS: Schizophrenic and comparison groups differed significantly in the amount of prepulse inhibition produced by the 16-dB prepulse, with schizophrenic patients showing the expected deficient prepulse inhibition. Latency of the eyeblink response was generally slower for the schizophrenic patients, but the prepulse-induced latency facilitation for schizophrenic patients and comparison subjects did not differ significantly. The pattern of prepulse inhibition deficits in schizophrenic patients remained, with age and education controlled, in an analysis of covariance and subgroup matching. Deficient prepulse inhibition correlated with both positive and negative symptoms of schizophrenia. CONCLUSIONS: Under these experimental conditions, schizophrenia-linked deficits in prepulse inhibition detected with a relatively strong prepulse are correlated with both positive and negative symptoms of schizophrenia. The level of correlation, while significant in this cohort, is not as robust as that in previous reports linking prepulse inhibition deficits with other measures, such as thought disorder. Future work should probably focus on the relationship of prepulse inhibition deficits to measures such as thought disorder rather than positive and negative symptoms.

Acoustic Stimulation↗

Eye blink reflexes to sudden free falls: a clinical test of otolith function.

Conventional neuro-otological tests measure only semi-circular canal function and not otolith function. A clinically acceptable test of otolith function was developed. Previous studies suggested that muscle responses which occur less than 100 ms after release into free-fall are part of a startle reflex originating in the otoliths. With a couch capable of producing sudden, safe, comfortable free-falls it was shown that in normal subjects orbicularis oculi muscle responses (that is eyeblinks) invariably began within 45 ms of this stimulus and confirmed that these eyeblink reflexes are part of a generalised startle reflex, as they cross-habituate with eyeblink reflexes elicited by supraorbital nerve stimulation. Eyeblink reflexes to free-fall may prove a useful clinical test of otolith function.

Adult↗

Subjective and physiological reactivity to chocolate images in high and low chocolate cravers.

Cue-reactivity to chocolate images was assessed using self-report and physiological measures. From a pre-screening sample of 454, young women were selected and assigned to high and low chocolate craving groups (N = 36/group). The experimental procedure consisted in the elicitation and measurement of the cardiac defense and startle reflexes while viewing chocolate and standard affective images selected from the International Affective Picture System. In response to chocolate images, high cravers reported more pleasure and arousal but less control than low cravers. In high cravers, viewing chocolate images inhibited the cardiac defense but potentiated the startle reflex, as compared to low cravers. The results confirmed at the physiological level that the motivational state that underlies the experience of chocolate craving include both appetitive (inhibition of the defense reflex) and aversive (potentiation of the startle response) components. The findings supported a motivational conflict theory of chocolate craving.

Adult↗

Effects of type I and type II pyrethroids on the startle response in rats.

The effects of type I and type II pyrethroids on the acoustic startle response of male Wistar rats were studied in three experiments. Pyrethroids were administered p.o. in 0.2 ml corn oil. In Expt. 1, techn. cis-permethrin (0, 30, 60, 90 mg/kg) and techn. cis, trans-cypermethrin (0, 60, 90, 120 mg/kg) increased startle in a dose-dependent way, whereas overt behavior and habituation of the startle response were not affected. In Expt 2, NAK 1901 (0, 1, 2.5, 4 mg/kg) enhanced startle amplitudes dose dependently and deltamethrin (0, 2, 4, 6 mg/kg) had no effect on startle. After both deltamethrin and NAK 1901 toxic signs increased dose dependently but an effect on potentiation of the startle reflex was not found. In Expt. 3, deltamethrin (0, 2, 4, 6 mg/kg) was administered and the highest dose attenuated startle amplitudes significantly, whereas toxic signs increased dose dependently. Deltamethrin had no effect on habituation of the startle response. It is concluded that type I pyrethroids increase the amplitude of the startle reflex; this effect does not depend on the presence of overt signs of toxicity. Type II pyrethroids have dissimilar effects on startle. Results are discussed suggesting that the effects of type II pyrethroids on startle amplitude are mediated by an indirect metabolic effect and a direct effect at the site of the muscle.

Animals↗

The auditory startle response in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) patients are considered to have excessive EMG responses in the orbicularis oculi (OO) muscle and excessive autonomic responses to startling stimuli. The aim of the present study was to gain more insight into the pattern of the generalized auditory startle reflex (ASR). Reflex EMG responses to auditory startling stimuli in seven muscles rather than the EMG response of the OO alone as well as the psychogalvanic reflex (PGR) were studied in PTSD patients and healthy controls. Ten subjects with chronic PTSD (>3 months) and a history of excessive startling and 11 healthy controls were included. Latency, amplitude and duration of the EMG responses and the amplitude of the PGR to 10 auditory stimuli of 110 dB SPL were investigated in seven left-sided muscles. The size of the startle reflex, defined by the number of muscles activated by the acoustic stimulus and by the amplitude of the EMG response of the OO muscle as well, did not differ significantly between patients and controls. Median latencies of activity in the sternocleidomastoid (SC) (patients 80 ms; controls 54 ms) and the deltoid (DE) muscles (patients 113 ms; controls 69 ms) were prolonged significantly in PTSD compared to controls (P < 0.05). In the OO muscle, a late response (median latency in patients 308 ms; in controls 522 ms), probably the orienting reflex, was more frequently present in patients (56%) than in controls (12%). In patients, the mean PGR was enlarged compared to controls (P < 0.05). The size of the ASR response is not enlarged in PTSD patients. EMG latencies in the PTSD patients are prolonged in SC and DE muscles. The presence of a late response in the OO muscle discriminates between groups of PTSD patients with a history of startling and healthy controls. In addition, the autonomic response, i.e. the enlarged amplitude of the PGR can discriminate between these groups.

Acoustic Stimulation↗

Startle responses in hereditary hyperekplexia.

BACKGROUND: Patients with hereditary hyperekplexia have excessive startle responses that are accompanied by transient stiffness and also continuous stiffness in infancy. A point of mutation has been identified for the major form of hereditary hyperekplexia in the gene encoding the alpha 1 subunit of the glycine receptor. OBJECTIVE: To measure startle reflexes and autonomic responses in the major form of hereditary hyperekplexia in the original Dutch pedigree. DESIGN: Startle reflexes and autonomic responses were examined by administering 3 series of 20 auditory stimuli at intervals of 10 seconds (90 and 113 dB) and 60 seconds (113 dB). SETTING: The Department of Neurology and Clinical Neurophysiology at the Leiden University Hospital, Leiden, the Netherlands. SUBJECTS: Nine patients with the major form of hyperekplexia and 20 healthy controls. Of the 9 patients, 5 took medication. The patients are part of the Dutch hyperekplexia pedigree. MAIN OUTCOME MEASURES: Startle responses were quantified with latency periods and areas of electromyographic bursts of the orbicular muscle of the eye, sternocleidomastoid and biceps muscles, and the thenar muscles. Autonomic reactions were measured with psychogalvanic responses and beat to beat changes of blood pressure and heart rate. RESULTS: The electromyographic bursts of the 4 muscles occurred in similar order in both patients and controls. The onset of the latency periods in the patient group was significantly (P < .001) prolonged in patients who took medication. Without medication, patients had shorter latency periods of the sternocleidomastoid muscle (P = .003) than controls. The electromyographic burst occurred significantly more often in patients than in controls (P < .001). The areas of the bursts were significantly larger in patients than in controls (P < .001); the degree of habituation was significantly stronger in patients than in controls (P < .001). The amplitude of the psychogalvanic response was increased in hyperekplexia, and the degree of habituation was significantly weaker in patients than in controls. Blood pressure and heart rate did not clearly react in either group. CONCLUSIONS: Motor startle responses are stronger and show more habituation in patients with hereditary hyperekplexia than in controls. The excessive responses include the psychogalvanic response. Increased responses do not necessarily indicate decreased habituation in hyperekplexia.

Acoustic Stimulation↗

Scopolamine reduces sensitivity to auditory gaps in the rat, suggesting a cholinergic contribution to temporal acuity.

Prior research [Caine et al., 1981] suggested that scopolamine, a central cholinergic antagonist, may increase gap thresholds in young human listeners. If confirmed, an effect of scopolamine on gap detection might help to explain why both aged humans and aged laboratory animals have less sensitive temporal acuity on gap detection tests, as they may be presumed to have less effective cholinergic mechanisms. Here we measured the effect of scopolamine on gap detection in rats (n=8) using reflex modification audiometry, which depends on the fact that brief gaps in noise presented immediately prior to a loud noise inhibit the acoustic startle reflex. Scopolamine increased the gap threshold and reduced reflex inhibition produced by gaps that were presented at and beyond about 40 ms prior to the startle reflex, but not at shorter lead times. A peripheral antagonist had no effect at long lead times. These data indicate that central cholinergic mechanisms are involved in relatively high level perceptual processing of gaps. This conclusion is consistent with the hypothesis that temporal acuity may be compromised in the aged listener because of deficits in the efficacy of these central mechanisms.

Acoustic Stimulation↗

The startle pattern in the minor form of hyperekplexia.

BACKGROUND: The major and minor forms of hereditary hyperekplexia (HE) are characterized by excessive startle responses, which are accompanied by transient stiffness only in major HE; patients with major HE also have continuous stiffness during infancy. A point mutation has been identified for major HE in the gene encoding the alpha 1 subunit of the glycine receptor but not for minor HE. OBJECTIVE: To measure startle reflexes and autonomic responses in the major and minor forms of HE in the original Dutch HE pedigree. DESIGN: Startle reflexes and autonomic responses were studied with 3 series of 20 auditory stimuli with intervals of 10 seconds (at 90 and 113 dB) and 60 seconds (at 113 dB). SETTING: A university hospital neurologic department. PATIENTS: Four patients with minor and 9 patients with major HE (patient groups) (a part of the Dutch HE family pedigree) and 20 healthy controls (control group). MAIN OUTCOME MEASURES: Startle movements were quantified with latencies and areas of electromyographic bursts of the following 4 muscles: the orbicular muscle of the eye, the sternocleidomastoid muscle, the biceps muscle of the arm, and thenar muscles. Autonomic reactions were measured with psychogalvanic responses. RESULTS. The 4 muscles contracted in similar order in the groups. The onset latencies of the orbicular muscle of the eye, the sternocleidomastoid muscle, and the biceps muscle of the arm were significantly prolonged in patients with minor HE (P < .006). The frequencies of occurrence of the electromyographic bursts were not different in the minor HE and major HE groups, but they were significantly higher in both patient groups compared with those in the control group (P < .001). The magnitude of the startle responses did not differ between the 2 patient groups (P = .4), but it was larger in both patient groups than in the control group (P < .001). Startle habituation in the minor HE group was much weaker than in the major HE group (P < .001) or in the control group (P < .001). The size of psychogalvanic responses (P = .1) and the degree of habituation (P = .24) in the minor HE group did not differ from those in the major HE group. Compared with that in the control group, the size of psychogalvanic responses in the minor HE group was larger (P < .001) and they habituated stronger (P < .001). CONCLUSIONS: The differences in the startle pattern between major HE and minor HE agree with the clinical and genetic findings: only major HE constitutes part of the HE phenotype. The cause of the minor HE is, as yet, unknown.

Adult↗

Temporal characteristics of enhancement of startle by stimulation of the amygdala.

A previous study demonstrated that electrical stimulation of the amygdala facilitated the acoustic startle reflex. The purpose of the present study was to determine the temporal relationship between activation of the amygdala and its enhancement of the acoustic startle reflex. A single 0.1 msec pulse was delivered to the central nucleus of the amygdala at various times before or after the onset of 20 msec noise burst or a 0.1 msec click. Startle was enhanced when the stimulation occurred within 5 msec of the startle stimulus onset. Electromyographic recordings from the neck muscles demonstrated that the short 6 msec latency startle response was facilitated even when amygdala stimulation was presented 1.25 msec after the onset of the startle stimulus. This indicates that the time for the effects of amygdala stimulation to reach the brain stem startle circuit is less than 5 msec, suggesting a very direct pathway from the amygdala to the startle circuit. The similarity of this effect to fear-potentiated startle is also discussed.

Acoustic Stimulation↗