Human Startle Response Research Articles

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

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

Amygdaloid N-methyl- d-aspartate and γ-aminobutyric acid A receptors regulate sensorimotor gating in a dopamine-dependent way in rats

Sensorimotor gating can be measured as prepulse inhibition of the startle response in humans and rats. Since prepulse inhibition is impaired in schizophrenics there is considerable interest in understanding the neuronal basis of prepulse inhibition. Neuropathological findings indicate a dysfunction of the glutamatergic and GABAergic system in cortico-limbic areas in schizophrenics. We tested whether blockade of N-methyl- d-aspartate or GABA A receptors in the basolateral amygdala affects prepulse inhibition in rats. Local infusion of the N-methyl- d-aspartate receptor antagonist dizocilpine (0, 6.25 μg/0.5 μl), or of the GABA A receptor antagonist picrotoxin (0, 5.0, 10.0 ng/0.5 μl) reduced prepulse inhibition. The prepulse inhibition-disrupting effect of 6.25 μg dizocilpine or 10.0 ng picrotoxin was reversed by systemic co-administration of the dopamine antagonist haloperidol (0.1 mg/kg i.p.). These data indicate that sensorimotor gating is regulated in a dopamine-dependent way by N-methyl- d-aspartate and GABA A receptors in the basolateral amygdala. Our findings are discussed with respect to neuropathological findings in schizophrenics.

Normalization of information processing deficits in schizophrenia with clozapine.

The authors tested the hypothesis that the use of an atypical drug, clozapine, for patients with schizophrenia is related to less impairment in information processing deficits (assessed by prepulse inhibition of the startle response) than is the use of typical antipsychotics. Two groups of schizophrenic patients--receiving either clozapine or a range of typical antipsychotics--were tested for prepulse inhibition (a reduction in response to a starting stimulus, if preceded briefly by a weak, nonstartling stimulus; measured at prepulse-to-pulse intervals of 30 msec, 60 msec, and 120 msec) of the acoustic startle response and compared with a group of healthy volunteers. Patients receiving typical antipsychotics showed less prepulse inhibition with 30-msec and 60-msec prepulse trials than did comparison subjects. Clozapine-treated patients showed normal levels of prepulse inhibition. Clozapine is superior to typical antipsychotics in normalizing prepulse inhibition, presumably because of its pharmacological effects on prefrontal regions of the brain or its effects on a broader range of neuroreceptors.

Prepulse Inhibition of theTritoniaEscape Swim

Presenting a weak stimulus just before a strong, startle stimulus reduces the amplitude of the ensuing startle response in humans and other vertebrates. This phenomenon, termed "prepulse inhibition" (PPI), appears to function to reduce distraction while processing sensory input. To date, no detailed neural mechanism has been described for PPI. Here we demonstrate PPI in the marine mollusk Tritonia diomedea, which has a nervous system highly suitable for cellular analyses. We found that a 100 msec vibrotactile prepulse prevented the animal's escape swim response to a closely following 1 sec tail shock. This inhibition was highly transient, with a significant effect lasting just 2.5 sec. These findings indicate that the Tritonia escape swim response undergoes a form of PPI phenomenologically similar to that observed in vertebrates. Further tests showed that the vibrotactile stimulus had no inhibitory effect if applied after tail shock, while the animal was preparing to swim, but it acted to terminate swims once they were actively under way. As a first step toward a cellular analysis of PPI, we recorded from neurons of the swim circuit in a semi-intact preparation and found that the vibrotactile stimulus used in the behavioral experiments also prevented the tail shock-elicited swim motor program. These results represent the first explicit demonstration of PPI in an invertebrate and establish Tritonia as a model system for analyzing its physiological basis.

Inhibition of the human startle response is affected by both prepulse intensity and eliciting stimulus intensity

The present study evaluated the effects of the intensity of prepulses and eliciting stimuli on the modification of the adult human acoustic startle eyeblink. Eyeblinks were elicited by 85, 95, and 105 dB(A) noise bursts, preceded on some trials by 60 or 70 dB(A) tones at a 120 ms stimulus onset asynchrony. Prepulse intensity was a within-subject variable in Experiment 1 ( N = 19) and a between-groups variable in Experiment 2 ( N = 38). For no-prepulse trials, as startle stimulus intensity decreased, startle amplitude, probability, and magnitude decreased, and startle latency increased. As startle stimulus intensity decreased from 105 to 95 dB, the amount of inhibition of response amplitude and magnitude remained stable for 70 dB prepulses in Experiment 1 and for both 60 and 70 dB prepulses in Experiment 2, whereas inhibition of response probability became more pronounced. As startle stimulus intensity decreased from 95 to 85 dB, prepulse inhibition of response amplitude and magnitude lessened and inhibition of response probability became still more pronounced in both experiments. These data show that the inhibition of startle can be affected by eliciting stimulus intensity, and that startle response amplitude and probability are affected by stimulus intensity changes in different ways.

Clinical and experimental characteristics of “hypothetically psychosis prone” college students

The study of individuals at the boundaries of schizophrenia has historically involved genetic relatives of schizophrenia patients or individuals who meet criteria for schizotypal personality disorder (SPD). Recently, many investigators have turned to the use of psychometric scales, developed to measure psychotic traits or vulnerability to developing schizophrenia, to screen large populations of college students in order to identify individuals who are “psychosis prone” or “schizotypal”. To help answer the question of whether students identified with psychometric scales are indeed psychosis prone, we screened 1115 college students with the Perceptual Aberration/Magical Ideation (PerMag) and Physical Anhedonia (PhysAn) Scales. Individuals who scored 2 standard deviations (SD) above the mean on the scales were selected as experimental subjects (N = 13 PerMag, N = 10 PhysAn) and a subpopulation of matched subjects who scored less than 0.5 SD above the mean were selected as control subjects (N = 24). All subjects then received a full battery of tests, including structured clinical interviews, the MMPI, and psychophysiological measures of information processing, including prepulse inhibition and habituation of the human startle response, visual backward masking and reaction time measures. The results suggest that the PerMag scale, but not the PhysAn scale, identifies individuals with some psychotic, affective and anxiety symptoms when compared to the controls. Neither scale predicts a diagnosis of schizotypal personality disorder or deficits on measures of information processing that characterize schizophrenia or schizotypal personality disordered patients.

Observing thought disorder and information-processing deficits in schizophrenia through parallel measurement

To better understand the possible relationship between impaired cognition and neurophysiological abnormalities in schizophrenia, new paradigms are needed. For example in the case of thought disorder, subjects are typically rated on the basis of their disordered cognition over some period of time, and at some later point tested on a series of neuropsychological or psychophysiological measures. To further our understanding of the cognitive impairments observed in schizophrenia we have reduced the temporal gap between measuring disordered cognition and neurophysiological processes by measuring the production of responses to the Rorschach (using Johnston and Holzman's TDI and Perry and Viglione's Ell) while measuring either skin conductance orienting responses (SCORs) or sensorimotor gating assessed via prepulse inhibition (PPl) of the human startle response. We have studied 15 schizophrenia patients exposed to a cornpater generated version of the Rorschach during which time they are presented with a I I$dB auditory startle pulse and a 74dB prepulse-I I$dB pulse pair. The PPi levels age assessed via EMG recording of orbicularis occuli muscles. Alternatively, subjects are presented with the Rorschach while their SCORs are recorded during their scanning of the stimuli. The findings allow for quantitative and qualitative analyses of the relationship between disordered cognition and information-processing deficits. Morcover, this design allows us to speculate about the neural circuit abnormalities associated with thought disorder as well as the relationship between impaired cognitive processes, which have a largely unknown neural basis, and measures of information-processing, which have a better understood neural basis.

Impaired startle prepulse inhibition and habituation in patients with schizotypal personality disorder.

Information processing measures that serve as biological markers for schizophrenia can help to define the boundaries of schizophrenia. Prepulse inhibition and habituation of the blink reflex component of startle, which are thought to reflect an individual's ability to screen out or "gate" irrelevant sensory stimuli, are impaired in patients with schizophrenia. These deficits in sensorimotor gating and habituation in schizophrenic patients may lead to sensory overload and, secondarily, cognitive fragmentation, disorganization, and thought disorder. The goal of this study was to test two hypotheses: 1) patients with schizotypal personality disorder would show a loss of sensorimotor gating reflected by impaired prepulse inhibition of the human startle response and 2) patients with schizotypal personality disorder would show deficits in startle habituation consistent with the deficits seen in patients with schizophrenia. Prepulse inhibition and habituation were assessed in 12 men and four women who met DSM-III-R criteria for schizotypal personality disorder and in 22 normal comparison subjects. Patients with schizotypal personality disorder had deficits in acoustic prepulse inhibition and habituation similar to the deficits observed in patients with schizophrenia. Although there were no differences between patients with schizotypal personality disorder and normal subjects in latency from acoustic startle stimuli to response, latency facilitation was produced by the prepulse in both groups. This pattern of changes in amplitude and latency of the startle response suggests that subjects with schizotypal personality disorder perceive the prepulse stimuli but still demonstrate deficient sensorimotor gating of amplitude. These findings support the importance of startle prepulse inhibition and startle habituation as biological markers for schizophrenia spectrum disorders.

From the jumping Frenchmen of Maine to post-traumatic stress disorder: the startle response in neuropsychiatry.

The startle response is a universal and phylogenetically ancient reflex. Pathological exaggerations and modifications of startle underlie the symptomatology of a surprisingly diverse range of neuropsychiatric disorders, a fact that seems to have gone largely unappreciated. We review the available literature on the physiology of the normal human startle response and examine the neuropsychiatric conditions characterized by pathological startle. Startle epilepsy and primary hyperekplexia are considered as neurological disorders involving abnormal startle. Patients with hyperstartle and exotic culture-bound syndromes characterized by excessive startle are considered by the authors to represent extreme variants of the normal startle response. Post-traumatic stress disorder, drug and alcohol withdrawal states and schizophrenia all have abnormal startle as a clinical feature secondary to increased arousal and presumed disturbance of central neurotransmitter systems. The neurophysiological mechanisms by which abnormalities of the startle response may occur are discussed and a system of classification of neuropsychiatric hyperstartles is suggested.

On Threat of Shock as an Elicitor of Anxiety: A Methodological Note

The effects of anxiety on the eyeblink component of the human startle response were measured in 32 college students. The manipulation of threat of shock was not successful in eliciting anxiety, suggesting that, while threat of shock can increase anxiety, this increase is not inevitable, illustrating the importance of a manipulation check of the effectiveness of the threat.

Modulatory Influence of Continuous Tone, Tone Offset, and Tone Onset on the Human Acoustic Startle Response

Startle modulation in young adult men, by continuous background tone and its offset, a 2-s sustained tone and its offset, and the onset of a 25-ms tone pip were compared. Tone (75dB 1000 Hz) offset and onset occurred either 2000 ms or 100-120 ms before the startle stimuli (104dB (SPL), 50-ms white noise bursts). Blink amplitude and latency were unaffected by continuous background tone. Blink amplitude was reliably inhibited by 100-ms offset of both the continuous background tone and the 2-s sustained tone or 120-ms onset of the tone pip, whereas effects on latency were more variable. Facilitation of blink amplitude and latency was significant but weak and only following the 2-s sustained tone, and only with respect to one of two experimental contexts. These findings support those of others and suggest that startle inhibition results from activation of neurons responding to transient environmental changes. The degree of inhibition appears to be related to stimulus value. Startle amplitude facilitation following long sustained prestimulation intervals is dependent on experimental context. Overall latency and amplitude modulation tend to be concordant, leading to the conclusion that the mechanism(s) underlying both are context dependent and linked in the adult human.

The startle response to acoustic stimuli near startle threshold: effects of stimulus rise and fall time, duration, and intensity.

ABSTRACTThe present study assessed the interaction of several stimulus parameters in the elicitation of the startle response in humans. Broadband noise stimuli with intensities of 80 and 85 dB(A) and durations of 30 and 50 ms were presented to four groups of 15 college undergraduates. Within subjects, stimulus rise and fall times of 2.5, 10, and 25 ms were presented in a 3 × 3 factorial design. Amplitude, probability, and latency of integrated EMG activity from orbicularis oculi (eyeblink) were assessed. As stimulus rise time increased, response amplitude and probability decreased, and response latency increased, for both durations and both intensities tested. A main effect of stimulus duration on response probability was found, with higher probability for 50‐ms than for 30‐ms stimuli. In conjunction with previous research which found no effect of stimulus rise time on startle responding with more intense stimuli, these results suggest that startle response elicitation is determined by an interaction of stimulus parameters, with manipulation of some parameters being more effective at certain levels of other parameters.