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Effects of thyrotropin-releasing hormone and its analogue L-6-ketopiperidine-2-carbonyl-leucyl-L-prolin-amide on behaviour and electroencephalogram.

A comparative dose-response investigation of thyrotropin-releasing hormone (TRH) and L-6-ketopiperidine-2-carbonyl-leucyl-L-proline-amide (RGH-2202) was carried out on rats and cats. RGH-2202 reduced the occurrence of photically evoked after-discharge in rats more significantly than TRH. Neither of the two compounds influenced the parameters of visually evoked potentials. Both compounds desynchronized the background electrocortical activity in rats. The amplitude of the acoustic startle reflex in rats was decreased dose-dependently only by RGH-2202, and this effect was nearly 3 times more potent than that of TRH. Both compounds increased the time spent awake, the latency to light sleep and the proportion of light sleep in a dose-dependent manner. The higher doses of TRH equalled the effects of the lower doses of RGH-2202. In cats the latency increasing effect of TRH on paradoxical sleep was about 30% less than that of RGH-2202; furthermore, the relative increase in the proportion of light sleep coupled with a corresponding decrease of deep sleep and paradoxical sleep was significant only in the case of RGH-2202. In a complex conditioned reflex situation in cats, the dose-dependent motivation decreasing effect on food intake and, as a consequence, on spontaneous motor activity was more pronounced in the case of TRH. The effective doses of RGH-2202 and TRH in rats were nearly equal, while in cats RGH-2202 showed about 1/10 of the potency of TRH. This finding suggests a considerably lower species variability of the effects of RGH-2202.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Paradox lost. The latah problem revisited.

This paper examines the validity of Dr. R. C. Simons' resolution (Simons, R. C. The resolution of the latah paradox. J. Nerv. Ment. Dis., 168: 195-206, 1980) of the so-called latah paradox. Latah, a Malay condition precipitated by sudden fright and involving compulsive obscenity and mimesis, was found to be closely related to local cultural values; yet a paradox seems to arise from the fact that analogous conditions are reported from unrelated cultures. Simons accounts for this by proposing that latah and its kindred states are based on the universal human startle reflex and that latah is merely a culture-specific exploitation of a neurophysiological potential shared by humans and other animals. It is here argued that the evidence does not support such a view and that latah-like conditions are best considered in terms of their local meaning within their societies of origin; ethnographic material from Siberia is examined as a case in point. It is concluded that the "latah paradox" is illusory and that biomedical approaches to the question have seriously misread the nature of the phenomenon and potentially distort clinical practice in relation to it.

Compulsive Behavior↗

Brainstem myoclonus.

In brainstem myoclonus, muscle jerks arise from activity in neuronal centres within the lower brainstem. The most common forms probably use the same circuitry as used by the normal startle reflex, which may be related to that described in animal experiments as the spino-bulbo-spinal reflex. In man, the jerks are generalized with long-lasting electromyographic bursts (greater than 100 ms), and may be provoked by many different types of sensory stimuli, although cutaneous taps around the nose and face are particularly effective. The neural activity spreads down from the brainstem via a relatively slowly conducting spinal efferent motor pathway. The cranial nerve nuclei are activated by rapid spread up the brainstem. Other forms of brainstem myoclonus may also exist, and these are characterized by more rapid conduction in spinal efferent pathways and greater sensitivity to muscle stretch rather than cutaneous input.

Animals↗

[Congenital hyperekplexia as a cause of neonatal hypertonia].

INTRODUCTION: Hyperekplexia is a disease characterized by an exaggerated startle reflex in front of minimal tactile and/or acoustic stimuli, that usually goes with high muscular tone, except when the patient is sleep. When the patient grows, high muscular tone decreases and then appear sudden hypertonic episodes that make fall the patient. Presence of inguinal and/or umbilical hernia is common, as well as sudden infant death. Neurophysiological findings can give guidance to diagnosis. It's an autosomal dominant transmission disease, but sporadic cases can appear. Clonazepam is the drug of choice, obtaining a marked improvement in a lot of patients. CLINICAL CASE AND CONCLUSIONS: Although rare, hyperekplexia is a diagnosis we must think about when we see an hypertonic newborn, and this is the reason why we report this case recently diagnosed in our hospital.

Anticonvulsants↗

Prefrontal cortex glucose metabolism and startle eyeblink modification abnormalities in unmedicated schizophrenia patients.

Attentional modulation of the startle reflex was studied in 16 unmedicated schizophrenia patients and 15 control individuals during the 18F-2-deoxyglucose uptake period for positron emission tomography. In a task involving attended, ignored, and novel tones that served as prepulses, control individuals showed greater prepulse inhibition (PPI) at 120 ms and greater prepulse facilitation at 4,500 ms during attended than during ignored prepulses; the amount of PPI and facilitation during novel prepulses was intermediate. In contrast, patients failed to show differential PPI at 120 ms and tended to show greater facilitation at 4,500 ms during novel prepulses. For control individuals, greater PPI was associated with higher relative metabolic activity rates in prefrontal (Brodmann Areas 8, 9, and 10 bilaterally) and lower in visual cortex. Patients showed this relationship only for Area 10 on the left. Patients also had low metabolism in superior, middle, and inferior prefrontal cortex. Consistent with animal models, our results demonstrate the importance of the functional integrity of prefrontal cortex to PPI modulation.

Acoustic Stimulation↗

Physiological abnormalities in hereditary hyperekplexia.

Five patients from a kindred with hereditary hyperekplexia had physiological testing. The surface-recorded electromyographic pattern of audiogenic muscle jerks was identical to that of the normal acoustic startle reflex. Testing at graded stimulus intensities indicated an increase in the gain of the acoustic startle reflex. Nose-tap stimuli resulted in short-latency generalized electromyographic bursts that were similar to the R1 component of the blink reflex. Electrical stimulation of peripheral nerves elicited a pattern of generalized muscle jerks that was similar to that of the acoustic startle reflex. Somatosensory evoked potentials, brainstem auditory evoked potentials, and cortical auditory evoked potentials were normal. The primary physiological abnormality in hereditary hyperekplexia is widespread elevated gain of vestigial withdrawal reflexes in the brainstem and possibly the spinal cord, most likely resulting from increased excitability of reticular neurons.

Acoustic Stimulation↗

Emotional imagery, the visual startle, and covariation bias: an affective matching account.

This study assessed the effects of imagery valence and arousal on the visually prompted startle reflex, heart rate, and estimates of probe occurrence in 24 males and 22 females. Valence and arousal independently augmented startle magnitudes, similar to prior research with acoustic probes (Witvliet, C.V.O., Vrana, S.R., 1995. Psychophysiological responses as indices of affective dimensions, Psychophysiology 32, 436-443). In both of these studies, arousal exerted stronger effects than valence on the startle reflex. Arousal also facilitated heart rate acceleration. Participants' estimates of startle flash occurrence reflected a covariation bias. Estimates were higher and more accurate for the high-arousal conditions and for the negative conditions, paralleling startle magnitude findings. Results suggest that affective response matching processes (rather than affective stimulus matching) influenced both startle reflex magnitudes and probe frequency estimates. Comparisons with the covariation bias literature are drawn, differences are addressed, and directions for future research are suggested.

Adult↗

Pharmacological dissociation of moderate and high contextual fear as assessed by freezing behavior and fear-potentiated startle.

The amplitude of the whole-body acoustic startle response is reliably enhanced when elicited in the presence of foreground signals, such as light, previously paired with footshocks. It has been shown that this enhancement is evident by moderate fear levels, but is less affected by high fear levels. Potentiation of the acoustic startle reflex has also been reported in the presence of background cues previously associated with footshocks. However, the effects of anxiolytic drugs on different levels of fear elicited by moderate and intense contextual fear conditioning associated with startle reflex have not been examined yet. To approach this issue, we examined the effects of the anxiolytic, midazolam, on two intensities of contextual fear; freezing behavior and the startle response to loud noise. First, we compared the magnitude of the freezing behavior and the startle amplitude during the testing sessions in groups of rats submitted to fear conditioning using 0.3 and 0.6 mA as unconditioned stimuli (10 stimuli of 1 s each, intertrial interval from 60 to 180 s). Afterwards, the effects of midazolam (0.5 and 1.0 mg/kg) were assessed in these two conditions. Rats showed a potentiated startle reflex and a significant freezing behavior to moderate fear conditioning, which were both attenuated by midazolam. Higher levels of fear conditioning caused more intense freezing behavior without enhancing the startle reflex. Whereas midazolam reduced this freezing response, the startle response was unaffected. These results are indicative that anxiolytic-sensitive freezing and fear-potentiated startle are triggered by moderate contextual fear conditioning, while contextual conditioning with the use of high footshocks causes a distinct pattern of behavioral responses, which is only partially affected by midazolam. Due to the differential sensitivity to midazolam of these two patterns of startle responses generated as a function of the intensity of contextual fear conditioning, it is proposed that they represent moderate and intense aversive states that may be related to anxiety or panic/phobic conditions, respectively.

Acoustic Stimulation↗

Startle response of human neck muscles sculpted by readiness to perform ballistic head movements.

1. An acoustic startle stimulus delivered in place of a 'go' signal in a voluntary reaction time (RT) task has been shown previously to advance the onset latency of a prepared distal limb movement without affecting the amplitude of the muscle response or movement kinematics. The primary goal of this study was to use muscles with a larger startle response to investigate whether the startling stimulus only triggered the RT movement or whether some form of interaction occurred between a startle response and a temporally advanced RT movement. 2. Twenty healthy male or female subjects were instructed to react as quickly as possible to an acoustic 'go' stimulus by performing a ballistic head flexion or right axial rotation. The 'go' stimulus was periodically replaced by an acoustic stimulus capable of eliciting a startle reflex. Separate startle-inducing stimuli under relaxed conditions before and after the movement trials served as control trials (CT trials). Bilateral surface electromyography of the orbicularis oculi, masseter, sternocleidomastoid and cervical paraspinal muscles, and head-mounted transducers were used to measure the muscle response and movement kinematics. 3. Muscle activation times in startled movement trials (ST trials) were about half those observed in RT trials, and were not significantly different from those observed in the startle CT trials. The duration of head acceleration was longer in ST trials than in RT trials and the amplitude of both the neck muscle electromyogram (EMG) and head kinematics was larger during ST trials than during RT trials. The EMG amplitude of ST trials was biased upward rather than scaled upward compared with the EMG amplitude of RT trials. 4. Over the 14 ST trials used in this experiment, no habituation of the reflex response was observed in the muscles studied. This absence of habituation was attributed to a combination of motor readiness and sensory facilitation. 5. The results of this experiment indicated that the neck muscle response evoked by a startling acoustic stimulus in the presence of motor readiness could be described as a facilitated startle reflex superimposed on a temporally advanced, pre-programmed, voluntary RT movement. Parallel reticular pathways to the neck muscle motoneurones are proposed as a possible explanation for the apparent summation of the startle and voluntary movement responses.

Adult↗

Differential blockade of early and late components of acoustic startle following intrathecal infusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or D,L-2-amino-5-phosphonovaleric acid (AP-5).

The present study investigated the individual contributions of spinal cord N-methyl-D-aspartate (NMDA) and non-NMDA receptors to the acoustic startle reflex in rats. The first experiment measured whole body acoustic startle before and after intrathecal infusion of various doses of either the NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid (AP-5), or the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Both compounds depressed startle in a dose-dependent fashion with similar potencies. A second experiment measured startle electromyographically (EMG) in the quadriceps femoris muscle complex in the hindlimbs during auditory stimulation to characterized the effects of these two compounds on the early (approximately 8 ms) or late (approximately 15 ms) EMG components of the startle response. CNQX preferentially blocked the early EMG component of startle, whereas AP-5 preferentially blocked the late component. These results suggest that the acoustic startle reflex involves an early EMG component mediated by spinal non-NMDA receptors, and a late EMG component mediated by spinal NMDA receptors.

2-Amino-5-phosphonovalerate↗

Startle gating deficits occur across prepulse intensities in schizophrenic patients.

The effects of prepulse stimuli of different intensities in inhibiting the startle reflex was assessed in 14 age-matched and gender-matched schizophrenic patients and 14 normal controls. The subjects were presented with startling stimuli consisting of bursts of white noise (106 dBA) with or without prepulse stimuli. Four intensities of prepulse stimuli were utilized: 75, 80, 85, and 90 dBA. Throughout the testing, the background noise was maintained at 70 dBA. The prepulse stimuli more effectively inhibited the startle reflex in the control group compared to the schizophrenic patients who showed deficient prepulse inhibition (gating) of the startle reflex. These results suggest that schizophrenics have impaired central inhibitory mechanisms over a fairly broad range of background noise to prepulse ratios. Further studies are needed to clarify exactly which ratios are optimal in eliciting prepulse inhibition (PPI) and in differentiating between schizophrenic and control groups.

Adult↗

Temporal acuity in auditory function in the rat: reflex inhibition by brief gaps in noise.

The acoustic startle reflex in the rat is inhibited if a relatively weak stimulus precedes the startle-eliciting tone burst. This research explored the effect of brief silent periods (gaps) in white noise on the startle reflex, in order to describe the limits of temporal resolution in the auditory system of the rat. Brief silent periods did depress reflex behavior, and two responsible processes were identified. One was most evident at a 190-msec lead time between gap and startle tone. It yielded a linear decrement in reflex expression over a dynamic range of 0-7 msec, and an estimate for the threshold of temporal acuity of 3.5 msec. The second was evident primarily at a 40-msec interstimulus interval and had a linear effect over a dynamic range of at least 40 msec. Very brief gaps had a greater inhibitory effect at the 190-msec interval between gap and startle stimulus; prolonged gaps had their greater effect at the 40-msec interval. The first process was identified as reflex inhibition, which is sensitive to the sensory properties of the lead stimulus. The second process was identified as sensory adaptation, produced by noise exposure but unmasked by silence.

Adaptation, Physiological↗

Latent inhibition of fear potentiated startle in rats.

Non-reinforced pre-exposure to a prospective conditioned stimulus impairs subsequent conditioning. This phenomenon is termed latent inhibition. In this report, we demonstrate latent inhibition in a classical conditioning procedure, the fear-potentiated startle reflex. Normally, the startle response is enhanced in the presence of a conditioned stimulus that has previously been paired with an aversive stimulus. We show that fear-potentiation of the startle response is significantly less pronounced in rats that have been repeatedly pre-exposed to a conditioned light stimulus. Similar to other procedures reported in the literature, the administration of the psychostimulant drug amphetamine (1.0 mg/kg) before pre-exposure and conditioning disrupts latent inhibition. A good deal is known about the neuronal mechanisms underlying the acquisition and expression of fear-potentiated startle, and therefore this new procedure could be a useful tool for investigating the neuronal basis of latent inhibition.

Acoustic Stimulation↗

Lack of startle modulation by smoking cues in smokers.

RATIONALE: The startle reflex methodology has been used to study the effects of nicotine in humans and the motivational effects of smoking cues in smokers. However, no other studies investigate startle modulation by smoking cues in smokers compared to non-smokers. In the other studies, smoking deprivation was manipulated in smokers or smokers were not compared directly to non-smokers. OBJECTIVE: The goal of this study was to examine the temporal course of information processing following the presentation of a smoking-related cue using the startle probe methodology in smokers compared to non-smokers. METHODS: Thirty-four smokers were selected on the basis of nicotinic dependence according to the DSM-IV, and compared to 34 non-smokers. During testing, subjects viewed neutral pictures and smoking related pictures displayed on a computer screen. Acoustic startle stimuli were delivered at various times after picture onset (60, 120 or 5000 ms) to examine inhibition by lead stimulus and the affective modulation of startle. RESULTS: The magnitude of startle reflex inhibition increased in smokers compared to non-smokers, at 60 and 120 ms. In all, there was no PicturexGroup interaction effect. CONCLUSION: We showed that smoking cues have no impact on the startle reflex of either group, even if, in line with previous results, prepulse inhibition was higher in smokers than non-smokers. These results suggest that smoking cues have no effect on the positive reinforcement of nicotine consumption, and that cognitive factors play a primary role in the development and maintenance of tobacco dependence.

Adult↗

The extended amygdala: are the central nucleus of the amygdala and the bed nucleus of the stria terminalis differentially involved in fear versus anxiety?

Although there is a close correspondence between fear and anxiety, and the study of fear in animals has been extremely valuable for understanding the neural basis of anxiety, it is also clear that a richer animal model of human anxiety disorders would include measures of both stimulus-specific fear and something less stimulus specific, more akin to anxiety. Patients with posttraumatic stress syndrome seem to show normal fear reactions but abnormal anxiety measured with the acoustic startle reflex. Studies in rats, also using the startle reflex, indicate that highly processed explicit cue information (lights, tones) activates the central nucleus of the amygdala, which projects to and modulates the acoustic startle pathway in the brain stem. Less explicit information, such as that produced by exposure to a threatening environment or by intraventricular administration of corticotropin-releasing hormone, may activate another part of the extended amygdala, the bed nucleus of the stria terminalis, which also projects to the startle pathway. Because this information may be less specific and of long duration, activation of the bed nucleus of the stria terminalis may mediate anxiety, whereas activation of the central nucleus of the amygdala may mediate stimulus-specific fear.

Amygdala↗

The effect of spatial separation of signal and noise on masking in the free field as a function of signal frequency and age in the mouse.

Masking of low- (4 kHz) and high-frequency (25 kHz) signals by one-octave bandpass maskers either spatially coincident with the signal or contralateral to it was examined in mice, 4-6 and 20-22 months of age, in the free field. Signals were presented 120 ms prior to a startle stimulus and differences in their inhibition of the startle reflex, relative to startle stimulus alone trials, were used to measure the severity of masking. Inhibition was reduced or eliminated by spatially coincident noise for weak but not for relatively intense signals, providing the type of "loudness recruitment" effect characteristic of human listeners in similar stimulus conditions. The spatial separation of the signal and its masker relieved this maskinglike effect for the high-frequency pair in both young and old mice. In contrast there was no beneficial effect of the shift in spatial location for the low-frequency pair at either age. This finding of masking release for high- but not low-frequency stimuli supports the hypothesis that the sound shadow provided by the head and pinna would yield a favorable signal-to-noise level difference for a contralateral masker and an ipsilateral signal only at very high frequencies in the mouse. The presence of masking release in these old mice, a first generation hybrid strain with near-normal high-frequency hearing in ABR measures, agrees with reports that the masking release resulting from a similar manipulation in aged human listeners with minimal high-frequency hearing loss is the equal of that obtained in the young listener.

Age Factors↗

A multi-process account of startle modulation during affective perception.

Modulation of the startle reflex by sensory, attentional, and emotional processes was explored by presenting acoustic startle probes at various delays following picture onset. Within 500 ms of onset, blinks were first greatly facilitated and then inhibited, indicating prepulse facilitation and prepulse inhibition that did not vary with affect. Attention allocation to the picture continued across the viewing interval and was most pronounced for emotional pictures, as determined by attenuation of the P3 component to the startle probe. Startle potentiation for unpleasant pictures occurred later in the viewing interval and was strongest for highly arousing pictures. Taken together, the startle reflex during picture viewing is modulated by sequential and sometimes concurrent processes of prepulse facilitation, prepulse inhibition, attentional inhibition, and affective modulation, with reflex magnitude reflecting the net effect of multiple processes.

Adult↗

Habituation of P300 and reflex motor (startle blink) responses to repetitive startling stimuli in children.

Positive EEG deflections with the latency and scalp distribution of the P300 accompany startle in response to loud auditory stimuli in a non-task context. The purpose of this investigation is to determine if habituation would have effects on the P300 similar to those on the startle blink. Thirty-four normal 7 to 11-year-old boys from a startle habituation study had EEG recordings of sufficient quality to provide data for the current study. Startle was measured both as orbicularis oculi EMG and vertical EOG and P300 was recorded at Pz in response to 40,104 dB bursts of white noise presented at 23-s intervals. Both the startle response and the P300 habituated toward asymptotic levels after the first 28 trials, suggesting that both startle and the subsequent cognitive evaluation of the startling stimulus, reflected in the P300 response, are modulated by a common neurophysiological mechanism extrinsic to the direct startle pathway. A modest significant correlation between the P300 and the vertical EOG peak latencies for the initial trials suggests that the cognitive evaluation of the startling stimulus may also include evaluation of the reflex response to that stimulus. Analyses of the within-subject associations between startle and P300 initial amplitudes and rates of habituation showed that these parameters varied independently within the individual subject, suggesting that the P300 is not a component of the startle response. Rather, it reflects an evaluation of the startling stimulus, decreasing in amplitude as the surprising value of the startling stimulus decreases with habituation.

Aging↗