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PubMed1992

Gating and habituation of the startle reflex in schizophrenic patients.

Schizophrenic patients exhibit impairments in both sensorimotor gating and habituation in a number of paradigms. Through human and animal model research, these fundamental cognitive deficits have well-described neurobiologic bases and offer insights into the neuroanatomic and neurotransmitter abnormalities that characterize patients with schizophrenic spectrum disorders. In this context, the startle response is particularly interesting, because it is a cross-species response to strong stimuli that is plastic or alterable using experimental and neurobiologic manipulations. Thirty-nine medicated schizophrenic patients and 37 normal control subjects were studied in a new electromyography based startle response paradigm in which both prepulse inhibition (an operational measure of sensorimotor gating) and habituation (the normal decrease in response magnitude to repeated stimuli over time) can be separated and assessed in one test session. The results indicate that schizophrenic patients have extensive deficits in both intramodal and cross-modal sensorimotor gating and a trend to show acoustic startle habituation deficits. The deficit in prepulse inhibition of startle amplitude exhibited by schizophrenic patients was evident when an acoustic prepulse stimulus preceded either an acoustic or a tactile startle stimulus. No deficit was observed in the prepulse-induced facilitation of startle latencies, indicating that the failure of gating was not due to a failure of stimulus detection. These findings suggest centrally mediated deficits in sensorimotor gating in schizophrenic patients.

Acoustic Stimulation↗
PubMed2004

Evidence of fearlessness in behaviourally disordered children: a study on startle reflex modulation.

BACKGROUND: Patterns of low heart rate, skin conductance and cortisol seem to characterise children with disruptive behaviour disorder (DBD). Until now, the startle paradigm has not been used in DBD children. We investigated whether DBD children, like adult psychopaths, process emotional stimuli in an abnormal way. METHOD: Twenty-one DBD and 33 normal control children viewed a series of 27 positive, neutral and negative slides. Startle probes were presented unpredictably during slide presentations and eye blink reflexes were measured. RESULTS: DBD and control children showed a similar linear relationship between slide valence and startle magnitude, but the startle-elicited blinks of the DBD children were significantly lower for all categories of slides. Moreover, the more delinquent the DBD children were, the lower their startle responses during unpleasant states. CONCLUSIONS: The results suggest a deficit in neurophysiological fear modulation. The implications of the findings for the fearlessness theory of antisocial behaviour are discussed.

Antisocial Personality Disorder↗
PubMed1988

Apomorphine, d-amphetamine, strychnine and yohimbine do not alter prepulse inhibition of the acoustic startle reflex.

Rats were presented with noise bursts alone or noise bursts 60 ms after presentation of either a 60 dB or an 80 dB prepulse after injection of the dopamine agonists apomorphine (3 mg/kg) or d-amphetamine (4 mg/kg), the glycine antagonist strychnine (1.5 mg/kg) or the alpha 2 antagonist yohimbine (5 mg/kg). Presentation of prepulses inhibited startle, with greater inhibition following an 80 dB versus 60 dB prepulse. Apomorphine, d-amphetamine and strychnine increased overall startle levels but did not attenuate prepulse inhibition, since the absolute change in startle following prepulse presentation was significantly greater after administration of these drugs. A lower dose of apomorphine also increased startle but had no effect on prepulse inhibition using test intervals of 10, 60, 100, 200 or 1000 ms. While these drugs did decrease per cent prepulse inhibition, this seemed wholly attributable to their increasing overall startle levels, rather than a real attenuation of prepulse inhibition. Yohimbine did not alter either startle baseline or prepulse inhibition. The results do not support the conclusion that overactivity of dopamine systems attenuates prepulse inhibition and, in addition, suggest that prepulse inhibition does not result from activation of either glycine or norepinephrine projecting to alpha 2 adrenergic receptors.

Acoustic Stimulation↗
PubMed2004

Two new neurophysiological indices of cocaine craving: evoked brain potentials and cue modulated startle reflex.

Craving for cocaine is one of the hallmarks of cocaine dependence. One of the problems with craving is its measurement. Traditional psychophysiological indices such as skin conductance and heart rate have yielded contradictory results. These measures of craving were found to correlate only moderately with self-reported craving. In the present study, event-related brain potentials (ERPs) and the cue modulated startle response (CMSR) are evaluated as indices for cocaine craving. Twenty-one abstinent cocaine-dependent subjects were divided into high and low cravers group based on the median split of self-reported craving scores. ERPs and CMSR were measured when subjects watched neutral, pleasant, unpleasant and cocaine-related pictures. Overall, it was found that cocaine-dependent subjects showed augmented slow-positive waves (SPWs) of the ERP on the cocaine pictures compared to neutral pictures. Only high cravers showed larger SPWs on the cocaine cues, suggesting an association between cue-elicited SPWs and self-reported cocaine craving. By contrast to the ERP measures, CMSR did not differentiate between cocaine pictures and neutral pictures. In addition, no differences between the low- and high cravers on the CMSR measure were found. The present results show that the evoked-potentials paradigm provides promising results to index cue-elicited craving. The use of startle modulation deserves further investigation.

Adult↗
PubMedDate not supplied

Mice lacking the UbCKmit isoform of creatine kinase reveal slower spatial learning acquisition, diminished exploration and habituation, and reduced acoustic startle reflex responses.

Brain-type creatine kinases B-CK (cytosolic) and UbCKmit (mitochondrial) are considered important for the maintenance and distribution of cellular energy in the central nervous system. Previously, we have demonstrated an abnormal behavioral phenotype in mice lacking the B-CK creatine kinase isoform, regarding exploration, habituation, seizure susceptibility and spatial learning. The phenotype in these mice was associated with histological adaptations in the hippocampal mossy fiber field size. Here, mice lacking the ubiquitous mitochondrial creatine kinase isoform (UbCKmit-/- mice) showed, when subjected to a similar battery of behavioral tasks, diminished open field habituation and slower spatial learning acquisition in the Morris water maze task, but normal sensory or motor functions. A reduced acoustic startle response, higher threshold, and lack of prepulse inhibition were observed in UbCKmit-/- mice, suggesting that the unconditioned reflexive responsiveness is not optimal. Our findings suggest a role for mitochondrial CK-mediated high-energy phosphoryl transfer in synaptic signalling in the acoustic signal response network and hippocampal-dependent learning circuitry of brain. Finally, we demonstrate that UbCKmit has a widespread occurrence in the cell soma of neuronal nuclei along the rostro-caudal axis of the brain, i.e. cortex, midbrain, hindbrain, cerebellum and brainstem, similar to the occurrence of B-CK. This may explain the similarity of phenotypes in mice lacking B-CK or UbCKmit. We predict that the remaining functional intactness of the cytosolic B-CK reaction and perhaps the compensatory role of other phosphoryl transfer systems are sufficient to sustain the energy requirements for basic sensory, motor and physiological activities in UbCKmit-/- mice.

Acoustic Stimulation↗
PubMed2004

Prenatal exposure of Long-Evans rats to 17alpha-ethinylestradiol modifies neither latent inhibition nor prepulse inhibition of the startle reflex but elicits minor deficits in exploratory behavior.

Prenatal administration of synthetic estrogens in humans as well as lower mammals was reported to alter behavior in adulthood. The alterations remain to be characterized according to specific pathophysiological hypotheses. In this study, three common behavioral models of schizophrenia were tested, i.e., latent inhibition (LI), prepulse inhibition of the startle response (PPI) and hyperlocomotion under amphetamine. Female Long-Evans rats were injected i.p. with a solution of 17alpha-ethinylestradiol (15 microg kg(-1)) everyday from day 9 to 14 of pregnancy, and behavioral characteristics of their offspring, raised by Wistar foster mothers, were compared to those of rats born from dams injected with the vehicle only, over the same gestation period. LI was tested in a conditioned taste aversion and a conditioned passive avoidance paradigm followed by a parametric study of PPI and an evaluation of locomotion in an open field under saline or amphetamine (1.5 mg kg(-1)). Histological brain measurements were also carried out in a subset of the same rats. Neither LI nor PPI was altered using methods that had proven sensitive in previous pharmacological studies. Treated rats' locomotion was impaired, but amphetamine did not elicit a differential enhancement. A thinner Amon's horn layer was observed in their hippocampus. This indicates that standard models of schizophrenia did not fit to the behavioral abnormalities found by others and confirmed in this study. They were not due to the abnormal maternal care to pups elicited by the treatment.

Amphetamine↗
PubMed2003

Enhancement of acoustic evoked potentials and impairment of startle reflex induced by reduction of GABAergic control of the neural substrates of aversion in the inferior colliculus.

The neural network of the inferior colliculus (IC), implicated in the generation of defensive behavior to aversive acoustic stimuli, is under tonic GABAergic control. Dopamine also seems to have a modulatory role in these neural circuits. It is still unclear how such changes in transmission of acoustic information influence the motor expression of the defensive behavior. Startle reaction to a sudden noise has been used as an effective way to measure the motor reactivity of rats to fearful acoustic stimuli. In this work we examined the processing of sensorial information--assessed by the recording of auditory evoked potentials (AEP)--and the behavioral effects--evaluated by the freezing and startle responses--during the reduction of GABA levels caused by microinjections of semicarbazide (SMC, 6 microg/0.2 microl), a glutamic acid decarboxylase inhibitor, into the IC. These data were compared to the effects of the overall arousal elicited by apomorphine (APO, 0.5 mg/kg, i.p.). The results obtained show that IC microinjections of SMC induced freezing behavior, enhanced the AEP and impaired the startle reaction to a loud sound. On the other hand, APO changed neither the AEP nor the startle in the same experimental conditions. These results suggest that the release of GABAergic control of the neural substrates of aversion in the IC results in an increased processing of auditory information along with an inhibitory influence on the motor pathways responsible for the startle response.

Acoustic Stimulation↗
PubMed1994

Slow cortical potential biofeedback and the startle reflex.

The negativity of slow cortical potentials (SCP) of the surface EEG is a measure of brain excitability, correlating with motor and cognitive preparation. Self-control of SCP positivity has been shown to reduce seizure activity. Following SCP biofeedback from a central EEG electrode position, subjects gained bidirectional control over their SCP. The current study used a modified feedback methodology, and found a positive relationship between negativity and magnitude of EMG startle response (a measure of cortical and subcortical arousal, particularly aversive response disposition). Greater success in SCP differentiation was associated with self-report of less relaxation during negativity training.

Adult↗
PubMed1977

Excitation of the common inhibitory motor neuron: a possible role in the startle reflex of the cockroach, Periplaneta americana.

The responses of the widespread common inhibitory motor neuron (CI) to tactile stimulation of the cercus and the abdomen and electrical stimulation of the cercal nerve and the abdominal connectives are investigated. Tactile stimulation produces high frequency (greater than 500 impulses/s) spike discharge in CI with the onset of CI activity preceding the discharge of the excitatory motor neurons. Electrical stimulation of the connectives demonstrates a monosynaptic connection between at least one intermediate sized fiber (conduction velocity =3.7 m/s) in the abdominal connective and the ipsilateral CIs in the meso-and metathoracic ganglia. Electrical stimulation of the cercal nerve suggests a disynaptic path from cercal nerve to CI. Arguments are presented for a cercal afferent-to-CI reflex and the possible functional role of early excitation of CI is discussed.

Animals↗
PubMed1997

Amygdala and bed nucleus of the stria terminalis: differential roles in fear and anxiety measured with the acoustic startle reflex.

Neural stimuli associated with traumatic events can readily become conditioned so as to reinstate the memory of the original trauma. These conditioned fear responses can last a lifetime and may be especially resistant to extinction. A large amount of data from many different laboratories indicate that the amygdala plays a crucial role in conditioned fear. The amygdala receives information from all sensory modalities and projects to a variety of hypothalamic and brainstem target areas known to be critically involved in specific signs that are used to define fear and anxiety. Electrical stimulation of the amygdala elicits a pattern of behaviours that mimic natural or conditioned states of fear. Lesions of the amygdala block innate or conditioned fear and local infusion of drugs into the amygdala have anxiolytic effects in several behavioural tests. Excitatory amino acid receptors in the amygdala are critical for the acquisition, expression and extinction of conditioned fear.

Amygdala↗
PubMed1999

Anesthetic profile of dexmedetomidine identified by stimulus-response and continuous measurements in rats.

This study characterizes the anesthetic profile of dexmedetomidine on the basis of steady-state plasma concentrations using defined stimulus-response, ventilatory, and continuous electroencephalographic (EEG) and cardiovascular effect measures in rats. At constant plasma concentrations of dexmedetomidine (range, 0.5-19 ng/ml), targeted and maintained by target-controlled infusion, the whisker reflex, righting reflex, startle reflex (to noise), tail clamp response, hot water tail-flick latency, and attenuation of heart rate (HR) increase associated with tail-flick (sympathoadrenal block) and corneal reflex, were assessed in 22 rats. EEG (power in 0.5- to 3.5-Hz frequency band), mean arterial pressure, and HR were recorded continuously. Blood gas values and arterial drug concentrations were determined regularly. The following steady-state plasma EC(50) values of dexmedetomidine (mean +/- S.E. nanograms per milliliter) were estimated: HR decrease (0.51 +/- 0.04), EEG (1.02 +/- 0.08), whisker reflex (1.09 +/- 0.10), sympathoadrenal block (1.85 +/- 0.80), mean arterial blood pressure increase (1.99 +/- 0.44), righting reflex (2.13 +/- 0.15), tail-flick latency (3.65 +/- 0.87), startle reflex (3.75 +/- 0.64), tail clamp (5.49 +/- 1.34), and corneal reflex (24.5 +/- 12.3). At the EC(50) value of tail clamp, ventilatory depression was minor. In rats, dexmedetomidine creates bradycardia, sedation/hypnosis, sympathoadrenal blocking effects, and blood pressure-increasing effects at plasma concentrations below 2.5 ng/ml. Higher plasma concentrations are needed to loose the startle reflex, tail-flick, tail clamp, and corneal reflex responses. Ventilatory depressant effects are minor. The applied EEG measure seems to reflect sedation/hypnosis but seems to have limited value to predict the deeper levels of analgesia and anesthesia of dexmedetomidine.

Analgesics, Non-Narcotic↗
PubMed2005

When good things go bad: the reflex physiology of defense.

For humans, the threat of painful shock greatly potentiates the reflexive startle blink. Moreover, viewing unpleasant, compared with pleasant, pictures also prompts heightened startle reflexes, suggesting that the startle reflex indexes general defensive activation. In this study, pleasant or unpleasant pictures were used to signal shock threat in order to explore how previous affective associations modulate new defensive reactions. When cuing threat of shock, pleasant and unpleasant pictures prompted physiological profiles consistent with defensive activation, indicating that threat of shock renders previously pleasant cues aversive. For unpleasant pictures only, defensive startle was potentiated even when these cues signaled safety. Taken together, the data indicate that (a) regardless of their intrinsic affective meaning, cues signaling shock threat prompt somatic and autonomic reactions consistent with defense, and that (b) intrinsically unpleasant cues continue to prompt defensive activation even when the context of their presentation is specifically non-threatening.

Adult↗
PubMed1996

Tracking early and late stages of information processing: contributions of startle eyeblink reflex modification.

Startle eyeblink modification was examined as a measure of information processing. College students were presented with tones of 5 and 7 s duration of either high or low pitch, followed by startle-eliciting stimuli at lead intervals of 120, 2,000, 4,500, or 6,000 ms. Attention to tones was manipulated by instructing the task group to count the longer tones of either pitch. The no-task group had no instructed task. Startle eyeblink was inhibited at the short lead interval and facilitated at the long lead intervals in both groups. The task group showed greater inhibition and facilitation during attended than during ignored tones, indicating that early and late controlled processing was occurring. In the task group, the degree of facilitation appeared to reflect the degree of cognitive demands of the task. Startle eyeblink modification may provide a sensitive measure of the nature and timing of stages of processing in active and passive attentional conditions.

Adult↗
PubMed1998

The effect of repeated prepulse and reflex stimulus presentations on startle prepulse inhibition.

The magnitude of a startle reflex is inhibited if the reflex-eliciting stimuli is preceded by a prepulse stimulus at a short lead interval. Previous research in humans has shown that the extent of prepulse inhibition decreases over repeated presentations of reflex stimuli and prepulse-reflex stimulus pairings. The present study (N = 70) investigated the effect of repeated presentations of prepulse stimuli, reflex stimuli, or prepulse-reflex stimulus pairings on prepulse inhibition. Five groups of subjects were presented during habituation training with either (a) reflex stimuli, (b) prepulse-reflex stimulus pairings, (c) a random sequence of prepulse and reflex stimuli, (d) prepulse stimuli, or (e) experimentally irrelevant light stimuli. Prepulse inhibition was reduced if startle stimuli were presented during habituation ((a), (b), (c)), but not after repeated presentation of the prepulse or the light stimulus ((d), (e)). The reduction in prepulse inhibition was abolished after dishabituation of the startle reflex. The present results indicate that habituation of the startle reflex can result in a reduction of prepulse inhibition.

Acoustic Stimulation↗
PubMed2006

Startle syndromes.

Startle syndromes consist of three heterogeneous groups of disorders with abnormal responses to startling events. The first is hyperekplexia, which can be split up into the "major" or "minor" form. The major form of hyperekplexia is characterised by excessive startle reflexes, startle-induced falls, and continuous stiffness in the neonatal period. This form has a genetic basis: mutations in the alpha1 subunit of the glycine receptor gene, GLRA1, or related genes. The minor form, which is restricted to excessive startle reflexes with no stiffness, has no known genetic cause or underlying pathophysiological substrate. The second group of startle syndromes are neuropsychiatric, in which excessive startling and various additional behavioural features occur. The third group are disorders in which startling stimuli can induce responses other than startle reflexes, such as startle-induced epilepsy. Diagnosis of startle syndromes depends on clinical history, electromyographic studies, and genetic screening. Further study of these disorders may enable improved discrimination between the different groups.

Humans↗