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PubMed1996

Effect of clonidine on the human acoustic startle reflex.

The present study investigated in healthy human volunteers whether clonidine reduced the amplitude of the acoustic startle reflex and whether this effect, if found, was due to an accelerated rate of habituation. Subjects were presented with startle-eliciting noise-bursts after intravenous (iv) infusion of clonidine (1.5 microgram/kg) and saline on separate days. Clonidine significantly reduced the amplitude of the acoustic startle reflex (as indexed by the eyeblink component) relative to the saline treated condition. This effect was neither due to an accelerated rate of habituation of the startle reflex nor to the sedative effect of clonidine. These findings complement an earlier report (Morgan et al. 1993) that yohimbine augments the amplitude of the startle reflex in man. Taken together, the two reports indicate a new model for the clinical investigation of central alpha2 adrenoceptor function in humans.

Acoustic Stimulation↗

PubMed2004

Prepulse inhibition of the acoustic startle reflex in pigs and its disruption by d-amphetamine.

Prepulse inhibition (PPI) of the startle reflex is an operational measure of sensorimotor gating. The dopamine receptor agonist-mediated disruption of PPI in rats is widely used as a model of the sensorimotor gating deficiencies demonstrated in schizophrenia patients. As a possible tool for validation of a pig model of psychosis, we wished to verify the existence of PPI in landrace pigs and investigate the potential disruption of PPI by d-amphetamine (AMPH) in these animals. PPI of the acoustic startle reflex and its potential disruption by AMPH were investigated using three doses 0.5-1.5mg/kg with a paradigm including two levels of prepulses (82 and 88dB) and a prepulse (PP) interval of 60 and 120ms. We found an average PPI of the startle reflex of 25.6% and both of the investigated PP intensities and PP intervals were equally effective in this PP-inhibitive paradigm. AMPH significantly disrupted PPI and, in spite of only the 0.5mg/kg dose proved statistically significant, the results indicate this to be dose-related. We have demonstrated the phenomenon of PPI of the startle reflex in landrace pigs and its disruption by d-amphetamine. Studies of sensorimotor gating defects could be a valuable additional tool in assessing pig models of neuropsychiatric disorders.

Acoustic Stimulation↗

PubMed2000

Using intracranial electrical stimulation to study the timing of prepulse inhibition of the startle reflex.

Due to the short latency and briefness of the startle reflex, event-related inhibition of startle has high temporal resolution and is useful for studying the hierarchical organization of sensorimotor gating and motive-motor gating. In this article, we describe methods for measuring the inhibitory effects of electrically stimulating each of the following four brain structures on startle in awake rats: the inferior colliculus (IC), the deeper layers of the superior colliculus (SC), the pedunculopontine tegmental nucleus (PPTg), and the ventral pallidum (VP). These four brain structures have been reported to be important in mediating sensorimotor or motive-motor gating. Startle responses are elicited by either intense noise bursts or electrical stimulation of the principal trigeminal nucleus. The time course of the IC-inhibited startle reflex is used as a standard for estimating timing of the neural transfer of startle-inhibitory information to motor outputs. We also discuss how these methods can be used in combination with neuropharmacology.

Animals↗

PubMed1991

The effect of posture on the normal and pathological auditory startle reflex.

The effect of posture on the EMG pattern of the normal auditory startle reflex was investigated. The startle response to an unexpected auditory tone was studied in eleven normal subjects when standing, and in six normal subjects when sitting relaxed or tonically plantar flexing both feet. Reflex EMG activity was recorded in the tibialis anterior and soleus about twice as frequently when standing, than when sitting relaxed. In addition, the median latencies to onset of reflex EMG activity in the tibialis anterior and soleus were about 40 and 60 ms shorter during standing, than when sitting relaxed. No short latency EMG activity was recorded in the calf muscles during tonic plantar flexion of the feet, while sitting. The effect of posture on the EMG pattern of the pathological auditory startle reflex was studied in five patients with hyperekplexia. In three patients the latency to onset of reflex EMG activity in the tibialis anterior was shorter when standing, than when sitting relaxed. The EMG pattern of the reflex response to sound was studied in detail in two of these patients and consisted of up to three successive components. The expression of each EMG component depended on the postural set of the limbs. In particular, a distinct short latency component was found in posturally important muscles following auditory stimulation. This short latency component was not recorded when sitting relaxed. It is concluded that the EMG pattern of the physiological and pathological auditory startle response is not fixed, but may change with the postural stance of the body. This finding supports the theory that the normal startle reflex and the abnormal startle reflex in hyperekplexia have a common brainstem origin.

Adolescent↗

PubMed1985

[Reticular structures of the cat brain participating in startle reflexes in response to somatic stimuli of different modalities].

Characteristics and reticular mechanisms of two types of late reflex responses (equivalents of the startle reflex) evoked by weak (tactile stimuli) and strong (high-threshold peripheral nerve stimulation) stimulations were studied in chloralose-anesthetized cats; these responses were designated as "tactile" (T) and "spino-bulbo-spinal" (SBS) reflexes, respectively. Some differences in the peripheral and central (brainstem) organization of these reflexes were found. In particular, the existence of the rostro-caudal differentiation of reticular structures involved in these types of reflexes was revealed using differential lesions of the brainstem reticular formation as well as its pharmacologic blockades (by means of microinjections of sodium chloride or procaine); the T-reflex was found to relay mainly through the pontine RF level, while the SBS-reflex--predominantly through the bulbar RF. Possible functional significance of the revealed differentiation in organization of some motor and sensory functions of the brainstem are discussed.

Animals↗

PubMed2000

Azimuthal directional sensitivity of prepulse inhibition of the pinna startle reflex in decerebrate rats.

Previous studies have indicated that the auditory midbrain, the inferior colliculus, is important for both sound localization and mediation of prepulse inhibition of the startle reflex. The present study investigated the azimuthal directional sensitivity of prepulse inhibition of the pinna startle reflex in decerebrate rats. The pinna startle reflex was measured by recording multi-unit action potentials from the cervicoauricular muscles. The startling noise burst (94 dB SPL) was produced by a stationary speaker at 0 degrees azimuth, and the non-startling prepulse noise burst (46 dB SPL) was produced by a movable speaker whose direction was changed in the frontal azimuthal plane. The interval between the onset of the prepulse sound and the onset of the startling sound was 100 ms. The pinna reflex to the startling sound was strongly inhibited by the prepulse sound, and the inhibited startle response exhibited a flat azimuthal directional curve. In addition to further confirming that the neural pathways mediating prepulse inhibition are located in the brainstem, the present results indicate that interaural disparities of binaural inputs used for sound localization are not capable of modulating prepulse inhibition of the startle reflex.

Acoustic Stimulation↗

PubMed1999

Modulation of the acoustic startle reflex by emotionally-toned film-clips.

It has been widely reported that the eyeblink component of the acoustic startle reflex can be modulated by emotionally-toned slide stimuli; pleasant slides reduce eyeblink amplitudes whereas unpleasant slides enhance them. The present study examines the modulation of the acoustic startle reflex by short (2-min) film-clips classified as pleasant, unpleasant or neutral, on the basis of subjective ratings. These film-clips were also evaluated with respect to their test-retest reliability in producing affective states as well as modulating startle reflexes. Overall, results showed significant reduction of startle during pleasant clips and augmentation during unpleasant clips. However, on first showing, one of the two unpleasant clips (a medical demonstration film depicting details of toe surgery) actually inhibited the startle reflex rather than augmented it. This is discussed in terms of the proposition that only stimuli which arouse fear can be guaranteed to augment startle; stimuli that are repulsive may produce perceptual and emotional 'blunting' that reduces startle amplitude.

Acoustic Stimulation↗

PubMed1998

Modulation of the acoustic startle reflex by infusion of corticotropin-releasing hormone into the nucleus reticularis pontis caudalis.

The amplitude of the acoustic startle reflex can be modulated by exposure to aversive stimuli or other conditions which evoke a state of fear. The neurotransmitters involved in this modulation are currently being investigated. Unilateral local infusion of corticotropin-releasing hormone (CRH; 0, 10, 20, 40 and 80 ng) into the nucleus reticularis pontis caudalis (PnC), an obligatory synapse in the acoustic startle reflex, significantly elevated startle amplitude in a dose-dependent manner. The facilitation of startle began immediately following infusion, reached asymptote approximately 20-25 min later, and persisted throughout the remaining 60 min test session. This CRH-enhanced startle effect was blocked by infusion of the CRH antagonist, alpha-helical CRH9-41, immediately prior to CRH infusion. These results support an involvement of CRH at the level of the PnC in modulating the acoustic startle reflex.

Acoustic Stimulation↗

PubMed1993

Emotion, novelty, and the startle reflex: habituation in humans.

Previous research with both animal and human subjects has shown that startle reflex magnitude is potentiated in an aversive stimulus context, relative to responses elicited in a neutral or appetitive context. In the present experiment, the same pleasant, unpleasant, and neutral picture stimuli were repeatedly presented to human subjects. Startle reflex habituation was assessed in each stimulus context and was compared with the habituation patterns of heart rate, electrodermal, and facial corrugator muscle responses. All systems showed initial differentiation among affective picture contents and general habituation over trials. The startle reflex alone, however, continued to differentiate among pleasant, neutral, and unpleasant pictures throughout the presentation series. These results suggest that (a) the startle probe reflex is relatively uninfluenced by stimulus novelty, (b) the startle modulatory circuit (identified with amygdala-reticular connections in animals) varies systematically with affective valence, and (c) the modulatory influence is less subject to habituation than is the obligatory startle pathway or responses in other somatic and autonomic systems.

Adult↗

PubMed2005

Opposite effects of tetanic stimulation of the auditory thalamus or auditory cortex on the acoustic startle reflex in awake rats.

The amygdala mediates both emotional learning and fear potentiation of startle. The lateral amygdala nucleus (LA) receives auditory inputs from both the auditory thalamus (medial geniculate nucleus; MGN) and auditory association cortex (AAC), and is critical for auditory fear conditioning. The central amygdala nucleus, which has intra-amygdaloid connections with LA, enhances startle magnitude via midbrain connections to the startle circuits. Tetanic stimulation of either MGN or AAC in vitro or in vivo can induce long-term potentiation in LA. In the present study, behavioural consequences of tetanization of these auditory afferents were investigated in awake rats. The acoustic startle reflex of rats was enhanced by tetanic stimulation of MGN, but suppressed by that of AAC. All the tetanization-induced changes of startle diminished within 24 h. Blockade of GABAB receptors in the LA area reversed the suppressive effect of tetanic stimulation of AAC on startle but did not change the enhancing effect of tetanic stimulation of MGN. Moreover, transient electrical stimulation of MGN enhanced the acoustic startle reflex when it lagged behind acoustic stimulation, but inhibited the acoustic startle reflex when it preceded acoustic stimulation. The results of the present study indicate that MGN and AAC afferents to LA play different roles in emotional modulation of startle, and AAC afferents are more influenced by inhibitory GABAB transmission in LA.

Acoustic Stimulation↗

PubMed2003

Genetic influences on prepulse inhibition of startle reflex in humans.

Prepulse inhibition (PPI) is a suppression of the startle reflex that occurs when an intense startling stimulus is preceded by a weaker 'prepulse' stimulus. PPI deficits have been implicated in the biological bases of schizophrenia and some other neuropsychiatric disorders and proposed as a possible biological marker (endophenotype) for genetic studies. However, little is known about the genetic determination of PPI in humans. We examined acoustic eye-blink startle reflex and PPI in 142 young female twins (40 monozygotic and 31 dizygotic pairs) and conducted a biometrical genetic analysis using structural equation modeling. PPI showed significant heritability suggesting that over 50% of PPI variance in this sample can be attributed to genetic factors. Baseline startle magnitude showed higher heritability (about 70%).

Acoustic Stimulation↗

PubMed1999

Comparison of the effects of diazepam on the fear-potentiated startle reflex and the fear-inhibited light reflex in man.

It has been shown previously that the amplitude of the acoustic startle reflex is enhanced, and the amplitude of the light reflex reduced, when subjects anticipate an aversive event, compared to periods when subjects are resting ('fear-potentiated startle reflex' and 'fear-inhibited light reflex'). We examined whether the anxiolytic diazepam would reverse the effects of threat on the startle and pupillary reflexes. Twelve male volunteers participated in three weekly sessions in which they received oral treatment with placebo, diazepam 5 mg and diazepam 10 mg, according to a balanced crossover double-blind design. One hour after ingestion of the treatments, miotic responses to light pulses and electromyographic responses of the orbicularis oculi muscle to sound pulses were elicited during alternating periods in which the threat of an electric shock (electrodes attached to the subject's wrist) was present (THREAT) and absent (SAFE). The THREAT condition was associated with a significant increase in the amplitude of the electromyographic (EMG) response, a significant reduction of the miotic response amplitude, and an increase in self-rated anxiety. Diazepam attenuated all these effects of THREAT. Diazepam did not affect the amplitude of the miotic response under the SAFE condition, but did suppress the EMG response under this condition. These results confirm the validity of the fear-potentiated startle reflex and fear-inhibited light reflex as laboratory models of human anxiety, and reveal some differences between the effects of diazepam on the two reflexes.

Acoustic Stimulation↗

PubMed2005

The acoustic startle reflex in Sprague-Dawley rats is altered by permanent middle cerebral artery occlusion.

The startle reflex is an unconditioned, quantifiable behavior used to study sensory modalities. We examined whether the acoustic startle reflex (ASR) was sensitive to lesions induced by focal cerebral ischemia. Sprague-Dawley rats were pre-screened for startle reflex responses 3-6 days prior to surgery and there were no differences in mean startle amplitude across groups. Animals were subjected to permanent middle cerebral artery occlusion (pMCAo) or a sham surgical procedure. Twenty-four hours later rats were evaluated for ASR prior to sacrifice. Infarct volumes were subsequently determined by quantitative image analysis of 2,3,5-triphenyltetrazolium chloride-stained brain sections. Infarct volumes of rats undergoing pMCAO ranged from 0 to 48%. Data were divided into three groups based upon percent infarction: mild (0-20%), moderate (21-35%), and severe (>35%). A within-subject analysis revealed a significant decrease in mean startle amplitude of only severely infarcted rats relative to their pre-surgery startle responses. Furthermore, the lesioned brain areas observed in these animals provide an anatomical basis for these results. Our findings demonstrate that ASR is affected in a model of stroke. Further work is needed to characterize this behavioral test and to determine whether it may have application as a surrogate endpoint for clinical stroke studies.

Acoustic Stimulation↗

PubMed1985

[Relay levels of acoustic and tactile startle reflexes in the reticular formation of the cat].

Reticular mechanisms of startle reflexes evoked by acoustic and tactile stimulation were studied in cat anesthetized with chloralose. Marked similarity in changes of both reflexes following surgical lesions and reversible hydrocompression blockade of the medial brain stem reticular formation structures were found. The data obtained evidenced for similarity of reticular substrates of these nonnociceptive reflexes (the pontine reticular formation, especially nucleus reticularis, pontis caudalis) in contrast to nociceptive spino-bulbo-spinal startle reflexes relayed mainly over the bulbar reticular formation.

Animals↗

PubMed2006

Prepulse inhibition (PPI) of auditory startle reflex is associated with PPI of auditory-evoked theta oscillations in healthy humans.

The aim of the current study was to investigate the auditory-evoked theta oscillatory activity associated with prepulse inhibition (PPI) of the startle reflex in healthy humans. Concurrent electroencephalogram (EEG) and auditory startle reflex were recorded from 19 healthy controls during Pulse-Alone and Prepulse + Pulse trials with 60, 120, and 240 ms prepulse-pulse intervals. Compared to Pulse-Alone trials significant PPI of the startle reflex occurred on all Prepulse + Pulse trials and a significant startle latency reduction occurred on 60 and 120 ms Prepulse + Pulse trials. The largest evoked potentials to auditory stimuli occurred at fronto-central locations. PPI of theta oscillations occurred at frontal, central, and parietal locations. These results suggest that PPI functions not only as sensory-motor gating but also as sensory-cognitive gating since theta oscillations are involved in control of cognitive processes. Absence of significant correlations between PPI of the startle reflex and of theta oscillations at all electrode locations indicates that the two processes may be controlled by different neural mechanisms.

Acoustic Stimulation↗

PubMed1990

Exaggerated startle reflexes in an elderly woman.

A 76-year-old woman with a 5-year history of excessive startle is reported. Electrophysiological recordings were made of muscle activation after acoustic and proprioceptive stimulation. The findings are discussed in relation to current knowledge of the startle reflex and classification of startle syndromes. It is concluded that this patient is best regarded as having a pathological exaggeration of the normal startle reflex rather than other causes of stimulus-sensitive muscle jerks.

Aged↗

PubMed2001

Brain stem circuits mediating prepulse inhibition of the startle reflex.

RATIONALE: Prepulse inhibition (PPI) of the startle reflex occurs when brief, non-startling tactile, acoustic or visual stimuli are presented 20-500 ms before the startling stimulus. OBJECTIVE: To review information about PPI-mediating brain stem circuits and transmitters, and their functions. RESULTS: Midbrain systems are most critical for the fast relay of these PPI stimuli. Acoustic prepulses for PPI are relayed through the inferior colliculus (IC). The superior colliculus (SC) is important for acoustic PPI, and may be important for the mediation of tactile and visual prepulses. This collicular activation for PPI is quickly relayed through the pedunculopontine tegmental nucleus (PPTg), with lesser contributions to PPI from the laterodorsal tegmental nucleus (LDTg) and substantia nigra, pars reticulata (SNR). The transient activation of midbrain nuclei by PPI stimuli is converted into long-lasting inhibition of the giant neurons of the caudal pontine reticular nucleus (PnC). We propose that muscarinic and GABA(B) inhibitory receptors (both metabotropic receptors) on PnC giant neurons combine to produce the long-lasting inhibition of startle. Activation of mesopontine cholinergic neurons leads to cortical arousal, turning and exploratory approach responses. CONCLUSION: PPI is mediated by a circuit involving the IC, SC, PPTg, LDTg, SNR and PnC. By reducing startle, PPI allows the execution of approach responses and perceptual processing following salient stimuli.

Acoustic Stimulation↗

PubMed1997

Emotional modulation of the startle reflex in twins: preliminary findings.

This study investigated twin similarity in general startle reflex reactivity and emotional modulation. Seventeen monozygotic (MZ) and 12 dizygotic (DZ) male twin pairs received startling acoustic stimuli while viewing emotionally positive, negative and neutral slides. Electromyographic (EMG) responses were recorded from the orbicularis oculi. Members of MZ twin pairs had similar response amplitudes under all three valence conditions. In addition, modulation scores for the positive and negative conditions, representing the percent change in response amplitude between the affective and the neutral conditions, also showed significant similarity within MZ twin pairs. Overall, members of DZ twin pairs were not found to be significantly similar of any of the measures. These preliminary findings suggest that emotional modulation of the startle reflex shows familial resemblance within MZ pairs. Given the lack of resemblance between DZ twins, it is tentatively suggested that affective modulation may be under partial genetic control.

Adolescent↗