The More or Less Startling Effects of Weak Prestimulation

Graham, Frances K.

doi:10.1111/j.1469-8986.1975.tb01284.x

Cited by 1,101 publications

(792 citation statements)

References 40 publications

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Section: Introductionmentioning

confidence: 99%

“…PPI of the startle reflex refers to an attenuation of this startle reflex that occurs when the evoking stimulus is preceded by a non-startling 'prepulse' by approximately 30-500 ms (Graham, 1975;Hoffman and Fleshler, 1963;Ison et al, 1973). In humans, the startle reflex is typically measured via the electrical activity of the orbicularis oculi muscle using electromyography (EMG) (Graham, 1975), and the PPI is typically calculated as a percentage score of the reduction in magnitude of this measure of the startle reflex, with maximal inhibition generally observed with 'lead intervals' of approximately 120 ms (Graham, 1975;Hoffman and Fleshler, 1963;Ison et al, 1973). It has now been well documented that patients with schizophrenia display a deficit in PPI (for a review see Cadenhead and Braff, 1999;Braff et al, 2001Braff et al, , 2007, which is interpreted as reflecting a failure of 'sensorimotor gating' (Braff and Geyer, 1990), and which may be normalized with the use of atypical antipsychotic drugs (Weike et al, 2000;Hamm et al, 2001;Kumari and Sharma, 2002;Kumari et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Mann

Croft

Scholes

et al. 2007

Neuropsychopharmacol

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Schizophrenia is associated with impairments of sensorimotor and sensory gating as measured by prepulse inhibition (PPI) of the acoustic startle response and P50 suppression of the auditory event-related potential respectively. While serotonin and dopamine play an important role in the pathophysiology and treatment of schizophrenia, their role in modulating PPI and P50 suppression in humans is yet to be fully clarified. To further explore the role of serotonin and dopamine in PPI and P50 suppression, we examined the effects of acute tryptophan depletion (to decrease serotonin) and acute tyrosine/phenylalanine depletion (to decrease dopamine) on PPI and P50 suppression in healthy human participants. In addition, we also examined for the first time, the effects of simultaneous serotonin and dopamine depletion (ie combined monoamine depletion) on PPI and P50 suppression. The study was a double-blind, placebo-controlled cross-over design in which 16 healthy male participants completed the PPI and P50 paradigms under four acute treatment conditions: (a) balanced/placebo control, (b) acute tryptophan depletion, (c) acute tyrosine/phenylalanine depletion, and (d) acute tyrosine/ phenylalanine/tryptophan depletion (combined monoamine depletion). Selective depletion of dopamine had no significant effect on either PPI or P50 suppression, whereas selective serotonin depletion significantly disrupted PPI, but not P50 suppression. Finally, the simultaneous depletion of both serotonin and dopamine resulted in significant reduction of both PPI and P50 suppression. We suggest these results can be explained by theories relating to optimal levels of monoaminergic neurotransmission and synergistic interactions between serotonergic and dopaminergic systems for normal 'gating' function. These findings suggest that a dysfunction in both serotonin and dopamine neurotransmission may, in part, be responsible for the gating deficits observed in schizophrenia, and their normalization following administration of atypical antipsychotic drugs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Mann

Croft

Scholes

et al. 2007

Neuropsychopharmacol

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“…PPI of the ASR is an attenuation of the startle amplitude by a non-startling prepulse preceding the startle-eliciting pulse by a certain amount of time, and is considered an operational measure of sensorimotor gating (eg Graham, 1975;Geyer et al, 1990;Swerdlow et al, 1994). Habituation is a reduction over time of the amplitude of the ASR, seen after repeated presentation of identical startle eliciting pulses, which is not a result of sensory adaptation or muscle fatigue, and is considered a form of non-associative learning (Christoffersen, 1997).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response

Jensen

Oranje

Wienberg

et al. 2007

Neuropsychopharmacol

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Sensorimotor gating is critical to normal brain functioning, and disruptions are associated with certain mental illnesses, such as schizophrenia. Prepulse inhibition of the acoustic startle reflex (ASR) (PPI) is an operational measure of sensorimotor gating, of which evidence for a serotonergic modulation is currently inconsistent. In a double-blind placebo-controlled crossover design, 18 healthy male volunteers received either placebo or a dose of 10 mg of escitalopram (SSRI), after which they were tested in both PPI and habituation of the startle reflex paradigms. No significant differences between the two treatments were observed on PPI, although escitalopram was found to significantly delay habituation of the ASR. In the current study, escitalopram was found to delay habituation, but it did not affect PPI in healthy male volunteers. As escitalopram is a highly specific SSRI, the results suggest that an increased serotonergic activity disrupts habituation, but not PPI in healthy volunteers.

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“…Another cross-species gating paradigm, prepulse inhibition of startle (PPI) is the focus of this review and differs qualitatively from the P50 ERP paradigm. Because it involves both sensory stimuli and motor responses (Graham, 1975), PPI is referred to as a measure of "sensorimotor gating" rather than sensory gating (Geyer and Braff, 1987;Braff and Geyer, 1990). In PPI, the acoustic startle response elicited by a sudden loud noise is measured in the presence or absence of a weak prepulse stimulus, which may be in the same or a different modality.…”

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confidence: 99%

The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

2006

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Prepulse inhibition (PPI) of startle is an operational measure of the pre-attentive filtering process known as sensorimotor gating. Originally identified in patients with schizophrenia, PPI deficits have been observed in multiple but not all psychiatric disorders. Thus, as with most signs and symptoms of psychiatric disorders, deficits in PPI cut across diagnostic categories. It remains unclear whether the diversity of disorders exhibiting deficient PPI bespeaks diagnostic overlaps or comorbidities. Given the recent focus on treatments for cognitive deficits of schizophrenia independently of treating psychosis, the relationship of PPI deficits to cognitive deficits becomes of interest. Although PPI cannot be considered to be a cognitive process per se, abnormalities in pre-attentive information processing may be predictive of or lead to complex cognitive deficits. Animal models of PPI deficits produced by dopamine agonists reliably predict existing antipsychotics. Nevertheless, since neither PPI nor cognitive deficits in schizophrenia are ameliorated by standard antipsychotics, current research is exploring the predictive value of non-dopaminergic PPI models in identifying treatments for gating disturbances independently of their relevance to specific disorders. Both PPI and cognitive deficits in schizophrenia patients are not reversed by first generation antipsychotics but may be attenuated by clozapine. Similarly, effects of glutamate antagonists on symptoms in patients and PPI in animals appear to be reduced by clozapine. Hence, treatment-induced reversals of deficits in PPI produced by glutamate antagonists may provide animal, and human, models to aid in the discovery of treatments of cognitive deficits in patients already treated with existing antipsychotics.

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The More or Less Startling Effects of Weak Prestimulation

Cited by 1,101 publications

References 40 publications

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response

The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

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