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Acoustic prepulses can facilitate the startle reflex in rats: discrepancy between rat and human data resolved.

Small changes in the sensory environment, called prepulses, prior to a startle-eliciting stimulus can inhibit or facilitate the startle reaction. Previous studies reported that at large intervals between prepulse and startle stimulus the prepulse facilitates the startle reaction, possibly by means of an orienting response. This was, however, only observed in humans and not in rats, and was consequently proposed to measure unique brain functions. In the present study with rats, the prepulse intensity was decreased from 85 to 81 dB, which resulted in decreased prepulse inhibition. Prepulse facilitation was now observed at large intervals (> 800 ms), which suggests that this facilitation was masked by inhibition in previous studies. These results solve the discrepancy between rat and human data and indicate that similar mechanisms are involved.

Acoustic Stimulation↗

Modification of the acoustic startle-reflex eyeblink: a tool for investigating early and late attentional processes.

The present experiment examined the sensitivity of short and long lead interval startle eyeblink modification to attentional processing. Eighteen college student subjects were presented with a series of intermixed high and low pitched tones and instructed to attend to tones of one pitch and to ignore tones of the other pitch. The majority of the attended and ignored tones served as prepulses for an eyeblink-eliciting burst of white noise presented at lead intervals of 60, 120, 240 and 2000 ms following prepulse onset. Results indicate that both attended and ignored prepulses produce significant startle eyeblink modification: significant blink inhibition at the 60, 120 and 240 ms short lead intervals, and blink facilitation at the 2000 ms long lead interval. In addition, compared with the ignored prepulse, the attended prepulse produced significantly greater blink inhibition at the 120 ms lead interval as well as significantly greater blink facilitation at the 2000 ms lead interval. These results suggest that both short and long lead interval startle eyeblink modification measures may be useful tools for future investigations of the early and later stages of attentional processing.

Acoustic Stimulation↗

Sex differences in sensorimotor gating of the human startle reflex: all smoke?

RATIONALE: A recent report described sex differences in the effects of nicotine use and withdrawal on prepulse inhibition of acoustic startle (PPI), but no sex differences in PPI in non-smokers. OBJECTIVE: To determine whether previously reported male>female acoustic PPI reflect sex differences in smoking effects on PPI, rather than simple sex differences in the regulation of PPI. A retrospective analyses of >600 carefully screened normals tested over the past 12 years was completed. RESULTS: Male>female acoustic PPI was detected in analyses that included: 1) all subjects; or 2) self-declared non-smokers. CONCLUSIONS: Sex differences in PPI cannot be accounted for by smoking history, because they are present across a large sample of non-smoking normal controls.

Acoustic Stimulation↗

Regionally selective effects of intracerebral dopamine infusion on sensorimotor gating of the startle reflex in rats.

Systemic administration of dopamine (DA) agonists markedly disrupts sensorimotor gating in rats as measured by prepulse inhibition (PPI) of the acoustic startle response. A qualitatively similar, but quantitatively weaker disruption of PPI follows DA infusion into the nucleus accumbens (NAC). The present study was designed to determine whether forebrain DA terminal fields other than the NAC contribute to the DAergic modulation of PPI. PPI was impaired significantly after infusion of DA (0-40 micrograms) into the NAC or anteromedial striatum, but not after DA infusion into the orbital cortex or posterolateral striatum. DA infusion into the amygdala also disrupted PPI, but this disruption was accompanied by a dose-dependent decrease in startle amplitude. These results suggest that DA overactivity in the both NAC and anteromedial striatum contribute to the gating-disruptive effects of systemically administered DA agonists, and that DA overactivity in mesocortical, mesoamygdaloid and "non-limbic" mesostriatal DA systems are not major substrates for a DAergic modulation of PPI.

Acoustic Stimulation↗

Immediate and long-lasting effects of chronic stress in the prepubertal age on the startle reflex.

The immediate and long-lasting effects of two models of chronic stress during the prepubertal period of life (21-32 days) on the acoustic startle response (ASR) were studied in outbred Wistar normotensives and rats with inherited stress-induced arterial hypertension (ISIAH) derived from them. Chronic variable stress (CVS) and repeated handling were used as chronic treatment. The obtained data showed a significantly attenuated ASR and a greater magnitude of prepulse inhibition (PPI) in juvenile and adult ISIAH compared to Wistar rats. The immediate effects of prolonged stress on the ASR were genotype-dependent. Young ISIAH rats exposed to both types of prepubertal stimulation had higher ASR than the age-matched controls. No significant stress-induced changes in the ASR were found in young Wistar rats. The long-lasting consequences of prolonged prepubertal stress were similar in the two strains and were determined by the specificity of stress stimulation: chronic handling had no effect on the ASR, while CVS enhanced it. The long-lasting effect of CVS experienced in prepubertal life appears to produce ASR changes similar to those seen in patients with posttraumatic stress disorder (PTSD). The magnitude of PPI increased from early age to adulthood and it was tolerant to environmental influences. The two rat strains did not differ in the rate of short-term habituation to repeated acoustic stimuli, which was unaffected by prepubertal stress. Evidence was obtained indicating that genetic and environmental background in childhood may contribute to the truncation of the startle response.

Aging↗

Effects of stress and shock anticipation on prepulse inhibition of the startle reflex.

The effects of shock anticipation and attention to external stimuli on prepulse inhibition (PPI) were compared. In the threat-of-shock experiment, acoustic startle stimuli were presented with and without prepulses when aversive shocks were or were not anticipated. In the control experiment, startle and prepulse stimuli were delivered during periods with attended or ignored external stimuli. In the threat-of-shock experiment, startle was potentiated (fear-potentiated startle) and PPI was increased by shock anticipation. A gradual reduction in the overall PPI throughout the experiment was also found. In the control experiment, only PPI was increased in the attend condition. The PPI level remained constant throughout the experiment. The increase in PPI in the threat and attend conditions may have resulted from an increase in the general level of alertness that facilitated the processing of the prepulse. The gradual decrease in PPI in the threat experiment was hypothesized to result from a progressive deficit in sensory functioning due to the stressful nature of repeated shock anticipation.

Acoustic Stimulation↗

The role of small changes in the acoustic environment in modifying the startle reflex.

When either the intensity or frequency spectrum of an approximately 70-db. SPL narrow-band noise was abruptly changed by a small amount, the rat's response to a startle stimulus presented 64 msec later was inhibited. When similar small frequency changes preceded the startle stimulus by ony 5 msec, the latency of the startle response was reduced, but even relatively large changes in intensity of the antecedent stimulus had no effect on response latency. These findings provide added support for the generalization that the neural processes associated with startle are engaged by small changes in the auditory environment. They also point to a measure of separation between the processes responsible for inhibition and those responsible for latency shift.

Animals↗

Role of the septum in the excitatory effect of corticotropin-releasing hormone on the acoustic startle reflex.

Intracerebroventricular administration of corticotropin-releasing hormone (CRH) elicits a constellation of behavioral, autonomic, and endocrinological changes typically observed in stress. One of the behavioral changes after intracerebroventricular CRH is a profound increase of startle amplitude (CRH-enhanced startle). The present study examined the role of the septum in CRH-enhanced startle. The septum has direct and indirect connections to the amygdala and inhibits the amygdala. Electrophysiological data show that CRH in the septum is inhibitory. Therefore, it has been hypothesized that intracerebroventricular CRH inhibits the septum, which in turn disinhibits the amygdala, resulting in a constellation of changes via activation of amygdala efferent targets. In testing this hypothesis, it was found that electrolytic lesions of the medial septum, but not the lateral septum, blocked CRH-enhanced startle. However, fiber-sparing chemical lesions of the medial septum did not block CRH-enhanced startle, suggesting that the blockade seen with the electrolytic lesions was caused by damage to fibers of passage. A major fiber bundle passing through the medial septum is the fornix, the primary efferent pathway for the hippocampus. Fimbria transection blocked CRH-enhanced startle almost completely, whereas the large electrolytic lesions of the dorsal hippocampus did not block CRH-enhanced startle. Taken together, these data suggest that perhaps the ventral hippocampus and its efferent target areas, which communicate via the fimbria, may be critically involved in CRH-enhanced startle.

Acoustic Stimulation↗

Habituation of prepulse inhibition of the startle reflex using an auditory prepulse close to background noise.

This study examined whether prepulse inhibition habituates with repeated presentation of the prepulse alone. Prepulse inhibition was determined by measuring the decrement in the startle response when the acoustic startle-eliciting stimulus was preceded by an auditory prepulse. Rats received repetitive exposures of the same auditory prepulse alone (experimental condition) and of a visual prepulse alone (control condition). To reduce habituation of startle itself and the possible dishabituating influence the startle stimulus might have on habituation of prepulse inhibition, startle stimulus presentations were infrequently interspersed among a much larger number of prepulse-alone presentations. Stimulus-specific habituation of prepulse inhibition occurred using an auditory prepulse 2.5 dB, but not 13 dB, above background noise. Implications are discussed for the role of prepulse inhibition in sensory gating.

Animals↗

On the feasibility to detect and to quantify prepulse-elicited reaction in prepulse inhibition of the acoustic startle reflex in humans.

The possibility that the prepulse stimulus typically employed in the studies of prepulse inhibition (PPI) can produce observable response has been questioned recently. Conflicting reports range from observations of prepulse-elicited startle reaction to a complete lack of detectable prepulse-elicited reactions in healthy volunteers. This controversy is subjected to critical examination in the present study. The ability of prepulse stimuli to induce PPI and to elicit measurable responses was examined in two separate experiments using prepulses ranging from 6 to 18dB above background (experiment 1), or 1 to 5dB above background (experiment 2). Three levels of pulse stimulus were employed: 95, 105 and 115dBA. Clear PPI and prepulse-elicited reaction were obtained in experiment 1, while neither effect was evident in experiment 2. Non-startle-eliciting prepulses that are of sufficient intensities to induce reliable PPI are associated with detectable and quantifiable response, confirming that direct evaluation of prepulse-processing is feasible and practical. This provides an additional measure of theoretical and potentially clinical relevance to PPI, and it ought to be included in future studies in patients as well as healthy subjects.

Acoustic Stimulation↗

Prepulse inhibition of the startle reflex: preliminary study of the effects of a low dose of alcohol in humans.

The present study was designed to examine the effects of a low dose of alcohol on prepulse inhibition (PPI) of the startle response and self-report measures of affect. Eighteen subjects participated in a counterbalanced repeated-measures design in which they received a beverage with alcohol during one session and a nonalcohol beverage during a different experimental session. The startle response was probed in two separate 10-min blocks immediately after consumption of the alcohol. Although alcohol significantly suppressed the startle response in general, it did not do so to an extent that compromised detection of PPI. The effects of alcohol on PPI were primarily evident in the first block and were dependent on baseline levels of PPI, such that alcohol resulted in a reduction of PPI in subjects who demonstrated low PPI at baseline and an increase in PPI for subjects with high PPI at baseline. Alcohol also significantly increased self-reported stimulation during the first block and increased negative affect during the second block. These findings suggest that baseline PPI may reflect an important individual difference that is predictive of the direction and magnitude of alcohol-induced changes in sensorimotor gating.

Adult↗

Acoustic startle reflex in schizophrenia patients and their first-degree relatives: evidence of normal emotional modulation.

We investigated emotional disturbances in 36 schizophrenia patients, 48 of their first-degree relatives, and 56 controls to determine if abnormal affective startle modulation could be associated with genetic risk for schizophrenia. Both patients and relatives had a pattern of startle modulation indistinguishable from controls, with potentiated startle amplitude while viewing negative valence slides and attenuation while viewing positive slides. Patients with flat affect did not differ from those without in startle modulation or slide ratings. The patients and their relatives had lower pleasantness ratings of positive slides and the patients had higher pleasantness ratings of the negative slides than controls. The startle paradigm may not be useful for identifying individuals with a genetic liability for schizophrenia. The results suggest that low-level defensive and appetitive behaviors are unaffected in schizophrenia.

Adult↗

Emotional-processing in posttraumatic stress disorder II: startle reflex modulation during picture processing.

This study examined the impact of a trauma-related stressor on subsequent emotional behavior in veterans with (n = 35) and without (n = 24) posttraumatic stress disorder (PTSD). Self-report and physiological responses, including acoustic startle, were recorded during viewing of emotionally evocative photographs at baseline and following exposure to trauma-related and non-trauma-related stressors. The 2 groups exhibited equivalent patterns of emotional response across self-report and physiological measures at baseline. In contrast, following the trauma challenge, participants with PTSD showed a pattern of startle modulation suggestive of greater defensive reactivity and reduced visual perceptual engagement. These findings, along with augmented corrugator EMG reactivity during the same interval, suggest that trauma-related reexperiencing primes subsequent negative emotional responding in individuals with PTSD.

Adaptation, Psychological↗

The effect of imipramine after single and repeated administration on the apomorphine response in the acoustic startle reflex in rats.

The paper presents the results of studies into the effects of single and repeated (2 or 10 mg/kg po, twice daily for 14 days) administration of imipramine (IMI) on the behavior of male Wistar rats in an acoustic startle response test. Statistically significant attenuation of the animal reactivity was observed after 8 or 14 days administration of IMI in a dose of 10 mg/kg. Apomorphine APO (1.0 mg/kg, ip) enhanced the animals reactivity after repeated (but not single) administration of IMI in a dose of 2 mg/kg. The obtained results confirm the hypothesis about an increase of the dopaminergic system reactivity under the influence of repeated administration of tricyclic antidepressants.

Acoustic Stimulation↗

EEG correlates of startle reflex with reactivity to eye opening in psychiatric disorders: preliminary results.

Previous studies have shown alterations of eyeblink reflex in patients with various psychiatric disorders. It has previously been demonstrated by our group that EEG measures of the reactivity to eye opening could effectively predict patient-reported startle response in patients with acute stress reaction. In our present study, EEG spectral power analysis and eyeblink electrical startle responses were acquired from a total of 39 patients diagnosed with various psychiatric disorders: 7 patients with schizophrenia, 10 patients with major depressive disorder (MDD), 10 patients with panic disorder, 5 patients with posttraumatic stress disorder (PTSD) and 7 patients with generalized anxiety disorder (GAD). EEG percent power data of each frequency band (delta, theta, alpha, beta) obtained from the 19 leads under open or closed eyelid conditions were used to calculate the arithmetical difference between eyes-open and eyes-closed states as representative of "EEG reactivity to eye opening". Data was analyzed separately for each diagnostic group. For all of the disorders, right-sided R2c (contralateral secondary component) latency was the single eyeblink startle measure that was found to be significantly correlated with EEG reactivity to eye opening. The correlation was most significant for right temporal theta frequency in schizophrenia, right temporal theta frequency in MDD, left central beta frequency in panic disorder, left parietotemporal delta frequency in PTSD and right occipital alpha frequency in GAD. Findings showed a newly identified pattern that has potential scientific and clinical value with respect to psychiatric medicine.

Adult↗

Differential motivational responses to food and pleasurable cues in anorexia and bulimia nervosa: a startle reflex paradigm.

BACKGROUND: Abnormal perceptions of food and shape underpin the cognitive behavioural model of eating disorders (EDs). The aim of this study was to investigate motivational processing of disorder-specific and standard emotional cues in anorexia (AN) and bulimia nervosa (BN) using startle eyeblink modulation (SEM). SEM was used because it is sensitive to motivational states of approach (appetitive response) and withdrawal (aversive response), which are independent of conscious intentional control. METHOD: Acoustically elicited SEM and subjective anxiety ratings were measured in 30 female patients with an ED (n=15 AN, n=15 BN) and 30 female control subjects while they viewed ED-relevant stimuli (food, female bodies) and standardized emotional pictures. RESULTS: BN subjects showed an appetitive response (startle inhibition) to food relative to neutral cues that differed significantly from AN subjects. By contrast, self-reports indicated significantly increased anxiety related to food cues across both ED groups. To female body picture (relative to neutral) cues, no significant between-group differences were found for SEM. ED subjects unexpectedly showed an aversive response (startle potentiation) to positive cues, in contrast to controls, who showed the established startle attenuation. CONCLUSIONS: These preliminary results suggest that BN patients demonstrated an exaggerated appetitive response to food but not to standardized positive cues, whereas SEM in AN patients points to a generalized failure to activate the appetitive motivational system. Differences in motivational salience to food cues are in line with distinctions between AN and BN in eating behaviour and food consumption and support differential treatment requirements.

Adult↗

Facilitation of the acoustic startle reflex by ponto-geniculo-occipital waves: effects of PCPA.

The relationship between ponto-geniculo-occipital (PGO) waves and motor activity during waking and non-rapid eye movement (non-REM) sleep stages was studied in cats treated with the serotonin synthesis inhibitor p-chlorophenylalanine (PCPA). PGO waves appeared in waking after daily treatment with PCPA. The magnitude of the acoustic startle elicited in the absence of prior PGO waves was increased (by a mean of 555%) by the PCPA treatment as compared to that of the pre-drug level. When startle-eliciting stimuli were presented shortly after the occurrence of the PGO wave, the response amplitude was further enhanced as compared to that of the baseline startle. The effect was maximal 50 ms following the peak of the PGO wave (average 192% of the baseline level), with return to the baseline startle level within 200 ms. A similar effect could also be seen with waking eye-movement potentials (EMPs) in drug-naive animals. Over half of the spontaneous PGO waves were found to be preceded or followed by discrete head-body movements. After PCPA, the amplitude of auditory-evoked LGN PGO waves increased during quiet waking (QW) while those in non-REM and REM sleep states did not change. It was concluded that serotonergic systems produce a tonic suppression of startle response and PGO amplitude in waking. PGO spikes in waking are associated with a phasic facilitation of the sensorimotor mechanisms involved in startle.

Acoustic Stimulation↗

Cytotoxic lesion of the medial prefrontal cortex abolishes the partial reinforcement extinction effect, attenuates prepulse inhibition of the acoustic startle reflex and induces transient hyperlocomotion, while sparing spontaneous object recognition memory in the rat.

The partial reinforcement extinction effect refers to the increase in resistance to extinction of an operant response acquired under partial reinforcement relative to that acquired under continuous reinforcement. Prepulse inhibition of the acoustic startle response refers to the reduction in startle reactivity towards an intense acoustic pulse stimulus when it is shortly preceded by a weak prepulse stimulus. These two behavioural phenomena appear to be related to different forms of attentional processes. While the prepulse inhibition effect reflects an inherent early attentional gating mechanism, the partial reinforcement extinction effect is believed to involve the development of acquired inattention, i.e. the latter requires the animals to learn about what to and what not to attend. Impairments in prepulse inhibition and the partial reinforcement extinction effect have been independently linked to the neuropsychology of attentional dysfunctions seen in schizophrenia. The proposed neural substrates underlying these behaviourial phenomena also appear to overlap considerably: both focus on the nucleus accumbens and emphasize the functional importance of its limbic afferents, including that originating from the medial prefrontal cortex, on accumbal output/activity. The present study demonstrated that cytotoxic medial prefrontal cortex lesions which typically damaged the prelimbic, the infralimbic and the dorsal anterior cingulate areas could lead to the abolition of the partial reinforcement extinction effect and the attenuation of prepulse inhibition. The lesions also resulted in a transient elevation of spontaneous locomotor activity. In contrast, the same lesions spared performance in a spontaneous object recognition memory test, in which the lesioned animals displayed normal preference for a novel object when the novel object was presented in conjunction with a familiar object seen 10 min earlier within an open field arena. The present results lend support to the hypothesis that medial prefrontal cortex dysfunction might be related to some forms of attentional abnormality central to the symptomatology of schizophrenia. Relevance of the present findings in relation to the neural substrates underlying the partial reinforcement extinction effect and prepulse inhibition is further discussed.

Acoustic Stimulation↗