Attentional Modulation Of Prepulse Inhibition Research Articles

Neural Correlates of Attentional Modulation of Prepulse Inhibition.

Prepulse inhibition (PPI) refers to the suppression of the startle reflex when the intense startling stimulus is shortly (20–500 ms) preceded by a weak non-startling stimulus (prepulse). Although the main neural correlates of PPI lie in the brainstem, previous research has revealed that PPI can be top-down modulated by attention. However, in the previous attend-to-prepulse PPI paradigm, only continuous prepulse but not discrete prepulse (20 ms) could elicit attentional modulation of PPI. Also, the relationship between the attentional enhancement of PPI and the changes in early cortical representations of prepulse signals is unclear. This study develops a novel attend-to-prepulse PPI task, when the discrete prepulse is set at 150 ms at a lead interval of 270 ms, and reveals that the PPI with attended prepulse is larger than the PPI with ignored prepulse. In addition, the early cortical representations (N1/P2 complex) of the prepulse show dissociation between the attended and ignored prepulse. N1 component is enhanced by directed attention, and the attentional increase of the N1 component is positively correlated with the attentional enhancement of PPI, whereas the P2 component is not affected by attentional modulation. Thus, directed attention to the prepulse can enhance both PPI and the early cortical representation of the prepulse signal (N1).

Spatial specificity in attentional modulation of prepulse inhibition of the startle reflex in rats.

Prepulse inhibition (PPI), the suppression of the startle reflex when the startling stimulus is shortly preceded by a weaker non-startling sensory stimulus (prepulse), can be enhanced by selective attention to the prepulse with a marked prepulse-feature specificity. To determine if the attentional modulation of PPI in rats can also be perceptual location specific, this study investigated whether fear-conditioning of a prepulse perceived at a location can enhance PPI only when the conditioned prepulse is perceived at that conditioned location. A continuous narrowband noise (NBN) was delivered by each of the two spatially separated loudspeakers in the frontal azimuth with a silent gap embedded in each NBN. The inter-loudspeaker interval was 1ms (either left or right loudspeaker leading). Due to the precedence effect, both the NBN and gap images were perceived at the leading loudspeaker. The perceptually fused gap was used as the prepulse. To fear-condition one gap prepulse, which was perceived at one loudspeaker, the prepulse was paired with footshock in a temporally precise manner and the other gap (the conditioning-control prepulse) perceived at the other (opposite) loudspeaker was paired with footshock in a random manner. Compared to PPI before conditioning, PPI induced by the fear-conditioned gap perceived at the fear-conditioned loudspeaker, but not that by the conditioning-control gap, was significantly enhanced. Thus, attentional modulation of PPI can be not only prepulse-feature specific, but also perceptual location specific, and involves combined central processes for content and location information.

The medial agranular cortex mediates attentional enhancement of prepulse inhibition of the startle reflex

The startle reflex, which interferes with on-going cognitive/behavioral activities, is of important protective function for humans and animals. Prepulse inhibition (PPI), as an operational measure of sensorimotor gating, is the suppression of the startle reflex in response to an intense startling stimulus (pulse) when this startling stimulus is shortly preceded by a weaker non-startling stimulus (prepulse). In both humans and laboratory animals, PPI can be enhanced by facilitating selective attention to the prepulse, suggesting that higher-order cognitive/perceptual processes modulate PPI. It has been well known that both the cholinergic system located in the basal forebrain and the deep layers of the superior colliculus in the PPI-mediating circuit are top-down modulated by the medial agranular cortex (AGm), which is a subdivision of the medial prefrontal cortex (PFC) and has wide axonal connections with both cortical regions (including the posterior parietal cortex) and subcortical structures critical for attention/orientation processes. This study investigated whether the AGm is involved in attentional modulation of PPI. The results showed that PPI was enhanced by fear conditioning of the prepulse, and then further enhanced by perceived spatial separation between the conditioned prepulse and a back-ground masking noise based on the auditory precedence effect. Bilateral injection of 2-mM kynurenic acid, a broad spectrum antagonist of glutamate receptors, into the AGm, but not the primary somatosensory cortex, eliminated these two types of attentional enhancement of PPI. Thus, the AGm plays a role in facilitating attention to the prepulse and is involved in the top-down modulation of PPI.

Both Val158Met Polymorphism of Catechol-O-Methyltransferase Gene and Menstrual Cycle Affect Prepulse Inhibition but Not Attentional Modulation of Prepulse Inhibition in Younger-Adult Females

Prepulse inhibition (PPI) can be modulated by both the Val158Met (rs4680) polymorphism of the Catechol-O-Methyltransferase (COMT) gene and the menstrual-cycle-related hormone fluctuations, each of which affects the subcortical/cortical dopamine metabolism. PPI can also be modulated by attention. The attentional modulation of PPI (AMPPI) is sensitive to psychoses. Whether the Val158Met polymorphism affects the AMPPI in female adults at different menstrual-cycle phases is unknown. This study examined whether AMPPI and/or PPI are affected by the Val158Met polymorphism in 177 younger-adult females whose menstrual cycles were mutually different across the menstruation, proliferative, or secretory phases. The AMPPI was evaluated by comparing PPI under the condition of the auditory precedence-effect-induced perceptual spatial separation between the prepulse stimulus and a masking noise (PPIPSS) against that under the condition of the precedence-effect-induced perceptual spatial co-location (PPIPSC). The results showed that both the menstrual cycle and the COMT Val158Met polymorphism affected both PPIPSC and PPIPSS, but not the AMPPI (difference between PPIPSS and PPIPSC). Moreover, throughout the menstrual cycle, both PPIPSC and PPIPSS decreased monotonously in Val/Val-carrier participants. However, the decreasing pattern was not overserved in either Met/Met-carrier or Met/Val-carrier participants. Thus, in healthy younger-adult females, PPIPSC and PPIPSS, but not the AMPPI, is vulnerable to changes of ovarian hormones, and the COMT Val158Met polymorphism also has a modulating effect on this menstrual-cycle-dependent PPI variation. In contrast, the AMPPI seems to be more steadily trait-based, less vulnerable to ovarian hormone fluctuations, and may be useful in assisting the diagnosis of schizophrenia in female adults.

Update of studies about prepulse inhibition in psychiatric disorders

Prepulse inhibition (PPI) is the suppression of the startle reflex when the startling stimulus is preceded by a non-startling stimulus (the prepulse). It is an operational measurement of sensorimotor gating mechanism to help the brain adapt to the complex environment, which could be top-down modulated by attention and other higher cognitive processes. Deficits of PPI and the top-down modulation of PPI are closely related to psychiatric diseases. Research papers published from January 2001 to October 2016 related to PPI in psychiatric disorders were searched in the Chinese and English databases. Results showed that schizophrenic patients and their relatives showed deficits in baseline PPI as well as the attentional modulation of PPI, and more importantly, the attentional modulation of PPI rather than the baseline PPI was more related to the symptom severity. Patients with Tourette’s syndrome showed PPI impairment, while patients with obsessive compulsive disorder had lower levels of PPI. PPI deficits in bipolar disorder patients were gender-dependent. Studying PPI and the top-down modulation of PPI could provide a basis to study the interaction of sensory processing and attention, and facilitate the researches of neural mechanism underlying the deficits of sensory gating. To establish advanced paradigms of PPI, new cognitive components could be introduced, such as attention, emotion, motor control, compulsivity and so on, thus improving the specificity of PPI test and promoting the PPI test as new biomarker and endophenotype in various psychiatric disorders. Key words: Prepulse inhibition; Schizophrenia; Tourette’s syndrome; Obsessive compulsive disorder; Bipolar disorder

Early attentional deficits in an attention-to-prepulse paradigm in ADHD adults.

Adults with attention-deficit/hyperactivity disorder (ADHD) were examined for early and late attentional processes as a function of controlled attention. The test paradigm was the attentional modulation of prepulse inhibition (PPI; early controlled attentional processing) and prepulse facilitation (PPF; late controlled attentional processing). In 49 patients and 49 controls, the authors measured acoustic startle responses to 96-dB startle pulses preceded 120, 240 (for PPI), 2,000, and 4,500 (for PPF) ms by a 68-dB prepulse noise. Geometric figures signaled that prepulses were to be ignored or attended to (automatic vs. controlled attention). ADHD patients exhibited deficits in prepulse modulation, but these reflected an interaction of controlled attention and time of information processing. Normal PPI and PPF occurred under all conditions except for controlled attentional modulation of PPI. Attention deficits in ADHD patients may reflect not general derangements in information processing or ability to attend but, rather, selective disturbances of controlled attention during early information processing.

Relationships between prepulse inhibition and cognition are mediated by attentional processes

Prepulse inhibition (PPI) is suggested to reflect a basic inhibitory mechanism which regulates sensory input to the brain, preventing sensory overload and cognitive fragmentation. However, studies directly investigating the relationship between PPI and cognition have produced inconsistent findings; this is likely to be due to the use of uninstructed PPI tasks, and limitations with the methods for measurement of PPI and startle. Therefore, the current study examined the relationship between cognitive performance and attentional modulation of PPI, using novel methods for the measurement of PPI. PPI was measured in 44 patients with schizophrenia and 32 healthy controls, across a range of startling stimulus intensities, under two attention set conditions. A range of neuropsychological tasks was also administered. Curves of best fit were fitted to the startle magnitudes, across the stimulus intensities, and a number of parameters were extracted from these curves, each of which reflects a different characteristic of the startle response. Correlations and quartile splits of the sample (highest versus lowest PPI) revealed that more PPI of response measures and less PPI of stimulus measures under the IGNORE condition was associated with superior performance in the colour-word subtest of the Stroop task. Further, more PPI of stimulus measures and less PPI of response measures under the ATTEND condition was associated with better performance on a memory task. These relationships appear to be mediated by common attentional processes active within both PPI and cognitive tasks, rather than by common underlying neurophysiological inhibitory processes.

Frontal–striatal–thalamic mediodorsal nucleus dysfunction in schizophrenia-spectrum patients during sensorimotor gating

Prepulse inhibition (PPI) refers to a reduction in the amplitude of the startle eyeblink reflex to a strong sensory stimulus, the pulse, when it is preceded shortly by a weak stimulus, the prepulse. PPI is a measure of sensorimotor gating which serves to prevent the interruption of early attentional processing and it is impaired in schizophrenia-spectrum patients. In healthy individuals, PPI is more robust when attending to than ignoring a prepulse. Animal and human work demonstrates that frontal–striatal–thalamic (FST) circuitry modulates PPI. This study used functional magnetic resonance imaging (fMRI) to investigate FST circuitry during an attention-to-prepulse paradigm in 26 unmedicated schizophrenia-spectrum patients (13 schizotypal personality disorder (SPD), 13 schizophrenia) and 13 healthy controls. During 3T-fMRI acquisition and separately measured psychophysiological assessment of PPI, participants heard an intermixed series of high- and low-pitched tones serving as prepulses to an acoustic-startle stimulus. Event-related BOLD response amplitude curves in FST regions traced on co-registered anatomical MRI were examined. Controls showed greater activation during attended than ignored PPI conditions in all FST regions—dorsolateral prefrontal cortex (Brodmann areas 46, 9), striatum (caudate, putamen), and the thalamic mediodorsal nucleus. In contrast, schizophrenia patients failed to show differential BOLD responses in FST circuitry during attended and ignored prepulses, whereas SPD patients showed greater-than-normal activation during ignored prepulses. Among the three diagnostic groups, lower left caudate BOLD activation during the attended PPI condition was associated with more deficient sensorimotor gating as measured by PPI. Schizophrenia-spectrum patients exhibit inefficient utilization of FST circuitry during attentional modulation of PPI. Schizophrenia patients have reduced recruitment of FST circuitry during task-relevant stimuli, whereas SPD patients allocate excessive resources during task-irrelevant stimuli. Dysfunctional FST activation, particularly in the caudate may underlie PPI abnormalities in schizophrenia-spectrum patients.

Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis

Patients with schizophrenia exhibit diminished prepulse inhibition (PPI) of the acoustic startle reflex and deficits in the attentional modulation of PPI. Pharmacological challenges with hallucinogens are used as models for psychosis in both humans and animals. Remarkably, in contrast to the findings in schizophrenic patients and in animal hallucinogen models of psychosis, previous studies with healthy volunteers demonstrated increased levels of PPI after administration of low to moderate doses of either the antiglutamatergic hallucinogen ketamine or the serotonergic hallucinogen psilocybin. The aim of the present study was to investigate the influence of moderate and high doses of the serotonergic hallucinogen N,N-dimethyltryptamine (DMT) and the N-methyl-D-aspartate antagonist S-ketamine on PPI and its attentional modulation in humans. Fifteen healthy volunteers were included in a double-blind cross-over study with two doses of DMT and S-ketamine. Effects on PPI and its attentional modulation were investigated. Nine subjects completed both experimental days with the two doses of both drugs. S-ketamine increased PPI in both dosages, whereas DMT had no significant effects on PPI. S-ketamine decreased and DMT tended to decrease startle magnitude. There were no significant effects of either drug on the attentional modulation of PPI. In human experimental hallucinogen psychoses, and even with high, clearly psychotogenic doses of DMT or S-ketamine, healthy subjects failed to exhibit the predicted attenuation of PPI. In contrast, PPI was augmented and the startle magnitude was decreased after S-ketamine. These data point to important differences between human hallucinogen models and both animal hallucinogen models of psychosis and naturally occurring schizophrenia.

Attention-dependent reduction in prepulse inhibition of the startle reflex in cannabis users and schizophrenia patients—A pilot study

Our previous report [Kedzior, K., Martin-Iverson, M., 2006. Chronic cannabis use is associated with attention-modulated reduction in prepulse inhibition of the startle reflex in healthy humans. J. Psychopharmacol. 20, 471–484.] indicates that chronic cannabis use in healthy humans is associated with deficits in the attentional modulation of prepulse inhibition of the acoustic startle reflex. The aim of the current study was to compare the attentional modulation of prepulse inhibition among healthy controls, otherwise-healthy cannabis users and schizophrenia patients (non-users) utilising the same attentional paradigm. Auditory startle reflex (the eye blink) was recorded from orbicularis oculi muscle while participants were attending to or ignoring 100 dB pulses and 70 dB prepulses separated by 20–200 ms. Cannabis users and schizophrenia patients showed a significant reduction in prepulse inhibition relative to controls while attending to, but not ignoring, auditory stimuli. These results suggest that the reduction in prepulse inhibition observed in cannabis users and in schizophrenia patients appears to be related to attentional dysfunction.

Attention and prepulse inhibition: the effects of task-relevant, irrelevant, and no-task conditions

We investigated whether attentional modulation of prepulse inhibition (PPI) is due to increased protection of processing of attended lead stimuli, decreased protection of processing of ignored lead stimuli, or a combination of both processes. Task and no-task trials, pre-cued by red and blue dots on a computer screen, were randomly intermixed. College student participants were instructed to do a tone duration judgment task on trials preceded by one color (task condition) and to do nothing on trials preceded by the other color (no-task condition). On task condition trials participants were instructed to count the number of longer duration tones of a particular pitch (attended condition) and to ignore tones of a different pitch (ignored condition). White noise startle stimuli were presented at 60 ms and 120 ms lead intervals on some trials in each condition. Additional startle stimuli were presented during the inter-trial intervals to measure baseline (unmodified) startle response. PPI in the attended condition was reliably greater than that in both the ignored and no-task conditions. PPI did not differ between the ignored and no-task conditions. The results are consistent with the conclusion that attentional modulation of PPI is due to increased protection of attended stimuli and not to decreased protection of ignored stimuli. Possible reasons for robust attentional modulation at the 60 ms lead interval as well as the usual 120 ms lead interval are discussed.

Attentional Modulation of Prepulse Inhibition: A New Startle Paradigm

There is increasing evidence for an influence of directed attention on prepulse inhibition (PPI) of the acoustic startle reflex. However, the existing paradigms for the assessment of this effect have methodological problems and pitfalls. In particular, most previous studies used a paradigm which directed the attention of subjects to the prepulse only. In the present study, we used a modified paradigm which directed the attention of the subjects both to the prepulse and the pulse. Twenty healthy male subjects were instructed trial by trial either to relax or to attend to the startle stimulus and decide whether it was a ‘simple’ (prepulse alone or pulse alone) or a ‘composite’ trial (pulse plus a prepulse or postpulse). Directed attention enhanced PPI at the lead interval of 240 ms, but not at the lead interval of 100 ms. This finding is in line with the idea that attention contributes to PPI when there is enough time for the attentional mechanisms to exert an influence. This new paradigm offers a valuable tool for the study of attentional modulation of sensorimotor gating in humans.

On the clinical and cognitive meaning of impaired sensorimotor gating in schizophrenia

Schizophrenia patients have been shown to have a defective sensorimotor gating process as indexed by impaired prepulse inhibition of the startle eyeblink reflex. Moreover, we have previously reported that schizophrenia patients have dysfunctional attentional modulation of prepulse inhibition. The present experiment combined our previous sample of 14 schizophrenia outpatients and 12 demographically matched control subjects with a new sample of 10 outpatients and 6 control subjects. All participants performed a tone-length judgement task that involved attending to one pitch of tone (the attended prepulse) and ignoring another pitch of tone (the ignored prepulse). During this task the acoustic startle eyeblink reflex was electromyographically recorded from the orbicularis oculi muscle. The results replicated the finding of impaired attentional modulation of prepulse inhibition in the new sample of schizophrenia outpatients compared to demographically matched control subjects. Specifically, the new control group exhibited greater startle modification during the attended prepulse, whereas the new patient group failed to show this differential effect. In addition, impaired prepulse inhibition following the attended prepulse was significantly correlated with heightened delusions, conceptual disorganization, and suspiciousness as measured with the expanded Brief Psychiatric Rating Scale. These correlations were significant with prepulse inhibition to the attended prepulse but not with prepulse inhibition to the ignored prepulse. Impaired prepulse inhibition was not correlated with negative symptoms. All in all, the results support the hypothesis that impaired attentional modulation of startle prepulse inhibition reflects basic neurocognitive processes related to thought disorder in schizophrenia.

Attentional modulation of startle in psychosis-prone college students.

Attentional modulation of startle eyeblink was studied in college students putatively at risk for psychosis and in normal controls. At-risk subjects had extreme scores on scales for either anhedonia or perceptual aberration-magical thinking (per-mags). Subjects were presented with to-be-attended and to-be-ignored tones; white noise startle probes were presented at lead intervals of 60, 120, 240, or 2,000 ms following the onset of attended and ignored tones and during intertone intervals. Controls showed greater inhibition of startle blink at 120 ms and greater facilitation at 2,000 ms during to-be-attended than to-be-ignored tone, demonstrating attentional modulation of prepulse inhibition and facilitation. Both at-risk groups showed normal overall levels of early inhibition and late facilitation. However, per-mags failed to show attentional modulation of either inhibition at 120 ms or facilitation at 2,000 ms; anhedonics showed no modulation of inhibition and modulation of facilitation was delayed in development. The results for the per-mags are strikingly similar to those observed in schizophrenic patients and suggest that these deficits index a trait-linked vulnerability to disorders in the schizophrenic spectrum.