Mounting evidence suggests involvement of prenatal factors in the pathogenesis of schizophrenia. The objective of the present study was to provide evidence for the hypothesis on schizophrenia that abnormal fetal brain development leads to impaired sensorimotor gating of acoustic startle stimuli. To this purpose, pregnant rats were treated with methylazoxymethanol acetate on one of four subsequent days of gestation, from E9 to E12. These procedures inhibit early stages of cortical proliferation in the foetuses, resulting in adult brain abnormalities that were mainly found in the entorhinal region. At the adult age, habituation andprepulse inhibition (PPI) of startle responses to acoustic stimuli were investigated. Our results show impaired habituation and PPI in rats treated at embryonic days 10 and 11. It is concluded that sensorimotor gating deficits can result from a developmental abnormality involving the entorhinal region, supporting the hypothesis that similar deficits, often observed in schizophrenic subjects, may be the result of entorhinal cortex dysfunction.

Schizophrenia and schizotypal personality disorder share common clinical profiles, neurobiological and genetic substrates along with Prepulse Inhibition and cognitive deficits; among those, executive, attention, and memory dysfunctions are more consistent. Schizotypy is considered to be a non-specific “psychosis-proneness,” and understanding the relationship between schizotypal traits and cognitive function in the general population is a promising approach for endophenotypic research in schizophrenia spectrum disorders. In this review, findings for executive function, attention, memory, and Prepulse Inhibition impairments in psychometrically defined schizotypal subjects have been summarized and compared to schizophrenia patients and their unaffected first-degree relatives. Cognitive flexibility, sustained attention, working memory, and Prepulse Inhibition impairments were consistently reported in high schizotypal subjects in accordance to schizophrenia patients. Genetic studies assessing the effects of various candidate gene polymorphisms in schizotypal traits and cognitive function are promising, further supporting a polygenic mode of inheritance. The implications of the findings, methodological issues, and suggestions for future research are discussed. (JINS, 2012, 18, 1–14)

Hypnosis involves the manipulation of conscious attentional discrimination. The prepulse inhibition (PPI) paradigm assesses primary unconscious information processing. We investigated the correlation between hypnotizability and PPI of the startle reflex. Forty-eight healthy subjects were evaluated with the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) and acoustic PPI. Subjects were divided into low, medium, and high hypnotizable groups. The low-hypnotizable group showed a significantly higher inhibition of the startle response, at lead intervals 60 ms and 120 ms, than did the medium- and high-hypnotizable groups. We conclude that hypnotizability and PPI may be negatively correlated. These findings lend further support for the role of dopaminergic neurotransmission mechanisms in the determination of hypnotizability levels.

Short-lead prepulse inhibition and long-lead prepulse facilitation of startle are greater during attended than ignored prestimuli. The present work examined whether this attentional modification is influenced by monetary incentive. Participants (43 college students) were randomly assigned to receive a small performance-based monetary incentive or were instructed to try their best. The task was to judge the duration of tones of one of two pitches during a series of 48 tones. Prepulse inhibition of startle eyeblink EMG was assessed at 60, 120, and 240 ms, and prepulse facilitation was assessed at 4,500 ms following tone onset. Short-lead percent prepulse inhibition was greater during attended than ignored prestimuli only at 120 ms among paid participants. Long-lead prepulse facilitation was greater for attended than ignored tones, but this effect did not vary with incentive condition. This study demonstrates that attentional modification of short-lead prepulse inhibition is sensitive to a monetary incentive and provides a basis for further examination of motivational effects on early attentional processing.

In adults, short-lead prepulse inhibition and long-lead prepulse facilitation of startle are greater during attended than ignored prestimuli. To examine these phenomena in children, fourteen 9- to 12-year-old boys completed a tone discrimination task in two sessions separated by 1 week. During each tone series, participants attended to one pitch and ignored the other. Startle probes (102 dB) were presented 120, 240, 2,000 or 4,500 ms following the onset of two-thirds of tones, and during one-third of intertrial intervals. Eyeblink EMG startle was recorded. Percent prepulse inhibition at 120 ms was greater for attended than ignored stimuli in Session 1 but not Session 2. Long-lead prepulse facilitation was marginally greater for attended than ignored tones and did not vary across sessions. Test–retest reliability was moderate during attended prestimuli but was modest during ignored prestimuli. Reliability of attentional modification was poorest at 120 ms and strongest at 4,500 ms. Overall, this study extended prior work in adults and provided a basis for further study of controlled attentional modification of startle in children.

This study of 31 college students employed the startle eye-blink modification (SEM) technique to index both early and later stages of attentional processing during a memory-load version of the Continuous Performance Test (CPT). Participants viewed a series of digits and pressed a button after the digit 7 of each 3–7 sequence. A startling noise burst was presented either 120 or 1,200 ms following three preselected prepulses: target (3), nontarget (non-3 and non-7 digits), or target plus distractor (3 and simultaneous tone distractor). Greater startle inhibition occurred 120 ms following target and target-plus-distractor prepulses compared with nontargets, indicating early selective attention. No difference was observed between SEM during target and target-plus-distractor prepulses, suggesting the distractor was effectively ignored. At 1,200 ms, the three prepulse types produced nondifferential inhibition, suggesting that modality-specific selective attention occurs in anticipation of the presentation of the next CPT prepulse. These findings indicate that SEM distinguishes between different early selective attention and later anticipatory attention subprocesses underlying the CPT.

Affective reactions to briefly presented pictures were investigated to determine whether fleeting stimuli engage the motivational systems mediating emotional responses. Emotional and neutral pictures were presented for 500 ms; heart rate, skin conductance, corrugator EMG, and the evoked startle reflex were measured. The time course of reflex modulation was similar to that obtained with longer (6 s) presentations, suggesting that picture processing continues in the absence of a sensory stimulus. Affective reactions found with more sustained presentation were also obtained, with more corrugator EMG activity for unpleasant pictures, and greater skin conductance reactivity for emotional pictures. Heart rate modulation, however, appears to rely on the presence of a sensory stimulus. The data also suggest that brief presentations of unpleasant pictures may result in less defensive activation than sustained presentation.

Prepulse inhibition (PPI) of the startle reflex is defined as the attenuation of the startle response to a startling stimulus (pulse), when such a stimulus is briefly preceded by a stimulus of subthreshold intensity (prepulse). PPI is thought to be neither learned nor due to conscious response inhibition, as it occurs at stimulus onset asynchronies (SOAs) too short to enable the activation of a volitional response. The present study explored the latter of these assertions by investigating (a) the degree to which human subjects are able to detect prepulses at SOAs of 30, 60 and 120 ms, and (b) whether such detection is related to inhibition. Startle eyeblink reflex and detection were measured in 39 participants subjected to an acoustic startle paradigm. Results revealed a significant trend in prepulse detection according to SOA, with highest detection rates at the 120-ms SOA (75%). However, trials on which detection occurred did not differ from trials without detection on measures of startle inhibition. This suggests that PPI is independent of awareness of the prepulse.

The effect of prehabituation of the prepulse on startle eyeblink modification was studied in two experiments. In Experiment 1, college student participants were either prehabituated or nonhabituated to a tone that served as a prepulse in a startle modification passive attention paradigm. Neither short lead interval (60 and 120 ms) prepulse inhibition (PPI) nor long lead interval (2,000 ms) prepulse facilitation (PPF) was affected by the prehabituation procedure. In Experiment 2, participants were presented with an active attention paradigm in which one of two tone prepulses was attended while the other was ignored. One group was prehabituated to the prepulses and the other was not. Unlike the results with the passive paradigm in Experiment 1, prehabituation did significantly diminish attentional modulation of PPI and PPF. These results are consistent with the hypothesis that passive PPI and PPF are primarily automatic processes, whereas attentional modulation involves controlled cognitive processing.

The effectiveness of different types of auditory prepulses in eliciting skin conductance orienting and in producing prepulse inhibition (PPI) of the acoustic startle eyeblink was studied in two experiments. A discrete white noise prepulse produced greater PPI than either a continuous white noise, a discrete tone, or a continuous tone. The discrete white noise advantage was not due to similarity in bandwidth to the startle pulse or to a refractory effect of the prepulse. Moreover, a dissociation between PPI and skin conductance orienting was seen in both experiments. PPI using auditory prepulses appears to be dependent primarily on the acoustic characteristics of the transient portion of the prepulse, whereas skin conductance orienting is more dependent on the sustained portions of the stimulus.

This study sought to determine whether prepulse inhibition and valence modulation of startle are independent, both within and across individuals. Acoustic probes (105 dB) were delivered as 68 undergraduates viewed pleasant, neutral, and unpleasant pictures. Weak acoustic stimuli (8 dB above background) preceded half of the probes by 120 ms. As expected, startles were larger during unpleasant than during pleasant pictures, and smaller on prepulse than no-prepulse trials. In general, valence modulation and prepulse inhibition of startle were unrelated. That is, prepulse inhibition was consistent across affective states, valence modulation did not differ between no-prepulse and prepulse trials, and valence modulation and prepulse inhibition effects were uncorrelated across individuals. Analysis of raw and percent modification scores generally led to similar conclusions. It is concluded that valence modulation and prepulse inhibition are independent startle modulatory phenomena, although this conclusion is tempered by a finding of poor internal consistency reliability for valence modulation.

Two experiments examined the effects of visually presented threat and nonthreat word lead stimuli on blink modification among unselected young adults (Experiment 1, N = 35) and participants selected for low and high trait anxiety (Experiment 2, N = 60). The blink reflex was elicited by a white noise probe of 105 dB. Lead stimulus intervals of 60, 120, 240, and 2000 ms were used in both experiments. Prepulse inhibition was observed at the 240-ms interval and prepulse facilitation was observed at the 60-ms interval in both experiments. Also, greater facilitation was found in both experiments during threat words at the 60-ms interval and greater inhibition during threat words at the 240-ms interval. Experiment 2 provided some evidence that the greater facilitation during threat words than during nonthreat words at the 60-ms probe interval may be found in high trait anxious participants, but not in low trait anxious participants. The results are discussed in relation to contemporary information processing theories of anxiety.

The temporal course of startle reflex modulation and autonomic response patterns to fear-relevant and fear-irrelevant pictures in subjects with high and low levels of animal fear was investigated. Thirty-eight high-fear and 48 low-fear volunteers viewed photos of snakes and spiders and pictures of neutral and pleasant content. The slides were presented for 6 s or for only 150 ms, depending on the group. Acoustic startle probes were presented at five different times after slide onset. Relative potentiation of the startle responses started 300 ms after onset of snake/spider pictures in fearful subjects. This fear-potentiated startle effect was maintained for the later probe times and was identical in the 150-ms condition. Fear-relevant pictures also prompted a sympathetically dominated autonomic response profile in fearful persons. These data support the idea that fear can be activated very rapidly, requiring only minimal stimulus input.

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.