Menstrual cycle phase effects on prepulse inhibition of acoustic startle

Prepulse inhibition (PPI) represents an attenuation of the startle reflex following the presentation of a weak prepulse at brief intervals prior to the startle eliciting pulse. It has been shown that increases in striatal dopamine levels decrease PPI; because dopamine release is sensitive to estrogen, it is likely that PPI varies across the menstrual cycle. Cross-sectional studies looking at estrogen effects suggest that this may be true. In this study, we compare effects of menstrual phase on PPI in a between-group design (men, follicular phase women, and luteal phase women) as well as a within-subjects design (women across the two phases). The study found a between-group as well as a within-subjects effect of phase on PPI. PPI in follicular phase women did not differ significantly from PPI in men. However, PPI was reduced in luteal women compared to follicular women. These data provide evidence that ovarian hormones affect sensorimotor gating.     

Habituation and sensitization of the acoustic startle response during cortical spreading depression in rats

Habituation of the acoustic startle response was tested in 8 groups of rats which received different CSD-treatments on 3 successive days. Both short-term habituation and long-term habituation were investigated. Bilateral CSD did have a significant effect on short-term habituation, but not unilateral CSD. This effect was interpreted as a temporary increment of sensitization in the beginning of the session. Neither unilateral CSD nor bilateral CSD had an effect on long-term habituation as long as no treatment change took place. Treatment change resulted in an increased startle amplitude if it was a change from no CSD to unilateral or bilateral CSD. The reverse change had no such effect. These results were interpreted as evidence for a gradual compensation over sessions for the initial CSD-induced sensitization increment. The results were discussed in connection with the results of earlier experiments on CSD and habituation.     

The varying time courses of attentional and affective modulation of the startle eyeblink reflex

In previous research on modulation of the startle eyeblink reflex, emotional effects have been demonstrated only at late probe positions, whereas attentional effects have been found at both early and late positions but only when the prepulses were affectively neutral. In Experiment 1, participants viewed emotionally valenced pictures and were instructed to attend to the duration of half of the slides. Affective modulation of the startle eyeblink occurred at long lead intervals, but attentional modulation also occurred late. In Experiment 2, participants viewed the same slides used in Experiment 1 but were instructed to attend to the duration of only the positive or the negative slides. Affective modulation occurred at both early and late probe positions, whereas attentional effects occurred only following slide offset. Early (250 ms) affective modification of startle eyeblink has not been previously reported. These results suggest that the time courses of emotional and attentional modulation of startle are variable and can occur at both early and late startle probe positions, depending on task requirements.     

Effects of background noise on the human startle reflex and prepulse inhibition

Three experiments investigated whether background noise modified the startle blink reflex and prepulse inhibition (PPI). In Experiment 1 background noise was about 28 (ambient), 40, and 60 dB; in Experiments 2 and 3 background noise was ambient and 60 dB. Prepulses were 70-dB tones (Experiments 1 and 3) or a tactile stimulus (Experiment 2). Startle-eliciting stimuli were 94-dB noise (Experiments 1 and 2) or an airpuff to the face (Experiment 3). Prepulses were presented at stimulus onset asynchronies of 30, 60, 120, 240, and 2000 ms relative to the startle-eliciting stimulus. Background noise of 60 dB had no effect on control reflexes, whereas 40-dB background noise increased control reflexes. Background noise decreased PPI, but only when an acoustic stimulus was used as prepulse. In sum, the findings show that background noise reduces the signal-to-noise ratio of acoustic prepulses and decreases their modulatory effect on the startle reflex.     

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.     

Affective modulation and prepulse inhibition of startle among undergraduates high and low in behavioral inhibition and approach

Valence modulation and prepulse inhibition of startle were examined among 80 undergraduates scoring in the upper and lower quartiles of self-report measures of behavioral inhibition (BIS) and behavioral approach (BAS). Participants viewed a series of pleasant, neutral, and unpleasant pictures. Acoustic startle probes (102 dB) were presented during most pictures and during intertrial intervals, and a prepulse (120-ms SOA) preceded half of the probes. Valence modulation on no-prepulse trials was greater among high-BAS than low-BAS participants. Consistent with theory regarding behavioral approach, post hoc tests demonstrated robust inhibition during pleasant versus neutral pictures among high-BAS participants, but not low-BAS participants. Valence modulation was reliable among high-BIS but not low-BIS participants, but the group difference was not significant. Contrary to our prediction, prepulse inhibition tended to be greater among high-BAS than low-BAS participants. The present data call attention to the role of individual differences in pleasant affective experience in startle modification.     

Prepulse modulation of the startle reaction and the blink reflex in normal human subjects

Blink reflexes are usually considered the most representative and consistent response of the auditory startle reaction (ASR), and they are often the only response evaluated in human psychophysiological studies. However, auditory stimuli also induce an auditory blink reflex (ABR), the physiological characteristics and brainstem circuitry of which may be different from those of the ASR. This study aimed to investigate whether there were differences between the orbicularis oculi (OOc) responses elicited with the ABR (OOcABR) and those elicited with the ASR (OOcASR) regarding their behavior to prepulse modulation. For comparison, we also examined the OOc responses to supraorbital nerve stimulation (OOcEBR). Electromyographic responses were simultaneously recorded from the OOc, masseter (MAS) and sternocleidomastoid (SCM) muscles. ABRs were considered when auditory stimuli induced responses limited to the OOc, and ASRs were considered when responses were induced in all muscles recorded from. Prepulse stimuli were either a weak electrical stimulation at the third finger (somatosensory prepulse) or a weak acoustic tone (auditory prepulse) that preceded the response-eliciting stimuli by intervals ranging from 0 to 200 ms. Prepulse effects differed according to prepulse modality, but the OOcABR and the OOcASR were always modulated in the same way. In both responses, somatosensory prepulses induced facilitation from 20 to 50 ms, followed by inhibition beyond 75 ms, and auditory prepulses induced no facilitation but a significant inhibition beyond 30 ms. In the OOcEBR, both somatosensory and acoustic prepulses induced facilitation of R1 and inhibition of R2 beyond 30 ms. Our results suggest that the OOcABR and the OOcASR exhibit the same physiological behavior regarding prepulse modulation. It is hypothesized that prepulse facilitation is due to direct impingement of subthreshold excitatory inputs onto the facial motoneurons while prepulse inhibition results from the engagement of a presynaptic inhibitory circuit in the brainstem. Received: 9 October 1998 / Accepted: 29 April 1999     

Effects of acute systemic 3-nitropropionic acid administration on rat activity and acoustic startle

Spontaneous activity, acoustic startle, and prepulse inhibition (PPI) of acoustic startle were measured in male Sprague–Dawley rats 3–5 h after 0, 10, 15, or 20 mg/kg i.p. 3-nitropropionic acid (3-NP), a mitochondrial toxin. Mean activity was significantly influenced by the 3-NP dose due to decreased activity for 20 mg/kg. Mean startle amplitude was not significantly affected by the 3-NP dose. Means of PPI for prepulses 6 and 12 dBA above background were smaller than means for respective 0 mg/kg doses, but the main effect of 3-NP dose did not reach statistical significance in ANOVA. The changes in measured exploratory-type activity and, possibly, in startle PPI parallel the occurrence of clinical signs exhibited at 3–5 h after 3-NP injection. Neural processing involved in these quantitative behavioral endpoints seems to be affected as energy stores are depleted and degenerative processes are beginning.     

Automatic and controlled attentional processes in startle eyeblink modification: effects of habituation 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 effects of prepulse inhibition timing on the startle reflex and reaction time

A loud acoustic stimulus has been shown to provoke a reflexive startle response and accelerate simple reaction times. However, an auditory prepulse presented in advance of a startling stimulus can reduce the effect of the startling stimulus. The current study examined the effect of the timing of the prepulse on startle-induced reaction times and the startle reflex. The task was to perform a 30° arm extension movement in response to a visual "go" stimulus. On selected trials, an auditory prepulse (80dB) was presented either 100ms, 500ms or 1000ms prior to the "go" signal. In addition, an auditory startling stimulus (124dB) was presented in conjunction with the "go" signal on some trials. Our results indicated that an auditory prepulse presented 100ms, and to a lesser extent 500ms, significantly decreased the amplitude of the startle reflex; however, the reaction time acceleration associated with the startling acoustic stimulus (SAS) was unaffected. The differential effect of the prepulse on the startle reflex and reaction time acceleration confirm different neural pathways for these effects while the differential effect of the prepulse on the control and startle RTs suggest different mechanisms for movement initiation.     

Relationship between prepulse inhibition of acoustic startle response and schizotypy in healthy Japanese subjects

Prepulse inhibition (PPI) of the acoustic startle reflex (ASR) is the most common psychophysiological index of sensorimotor gating. Several studies have investigated the relationship of PPI of ASR to schizotypy in Caucasians. However, little has been reported on this relationship in Asians. We investigated a possible relationship between PPI of ASR and schizotypy in 79 healthy Japanese subjects. Schizotypy was assessed by the Schizotypal personality Questionnaire (SPQ). PPI was evaluated at signal‐to‐noise ratios (SnRs: difference between background noise intensity and prepulse intensity) of +12, +16, and +20 dB. The total SPQ score, cognitive/perceptual score, and interpersonal score correlated negatively with PPI at SnR of +16 and +20 dB. We conclude that PPI is associated with the trait of schizotypy in healthy Asian subjects.     

Effects of cigarette smoking on prepulse inhibition, its attentional modulation, and vigilance performance

Startle eyeblink modification was measured during a degraded stimulus continuous performance test following both smoking and overnight abstinence among student smokers to measure the effects of smoking on both early and late attentional processes. A group of nonsmokers was tested twice without nicotine manipulation. A startling noise was presented either 240 or 1200 ms following target and nontarget stimuli presented during the task. Startle inhibition at 240 ms was greater following targets than nontargets following smoking and during both nonsmoker tests, but this attentional modulation was absent following abstinence. At the 1200-ms probe position, target and nontarget stimuli produced nondifferential inhibition during both tests for both groups. Abstinence among smokers produced reliably lower vigilance performance compared to ad lib smoking. The results indicate that smoking abstinence affects the early stages of stimulus processing.     

Attenuation of the prepulse inhibition of the acoustic startle response within and between sessions

Prepulse inhibition (PPI) and habituation of the acoustic startle response (ASR) are widely used biological markers in the study of psychiatric disorders and have been shown to be homologous across species. Previous studies in humans suggested that PPI is a stable and reliable measure between test sessions, but that PPI decreases within sessions. The purpose of this study was to explore the short- and long-term decrease in PPI as a potential confound in the measurement and interpretation of PPI. We investigated the progression of PPI and habituation of ASR in three test sessions spaced 4 weeks apart in a group of 20 healthy participants. Analysis revealed a significant decrease in the percent PPI within and between the test sessions. Nevertheless, PPI was reliable across three test sessions, indicating that the significant attenuation of PPI over time was a consistent phenomenon. These results suggest that PPI exhibits short- and long-term attenuation.     

Effects of a startle stimulus on response speed and inhibition in a go/no‐go task

Two studies examined the interaction of an acoustic startle stimulus and visual go/no‐go task stimuli on startle reactivity and task performance. In the first study, an acoustic stimulus (50 ms, 100 dB noise) was presented alone or with a green (go) or red (no‐go) circle; in the second study, a prepulse (50 ms, 75 dB noise) was presented alone or 120 ms before the startle stimulus or circle. The startle stimulus speeded responses to the go stimuli and increased the covert false alarm rate in the no‐go condition (measured by EMG activity in the hand), although very few overt errors were made in the no‐go condition. Startle response magnitude was increased by a circle but decreased by a prepulse. The speeding of go responses caused by a startle stimulus was attenuated by the occurrence of a startle response, suggesting that an intense accessory stimulus can facilitate responding to an imperative stimulus, and that the startle response to that intense stimulus can interfere with that facilitation.     

Plasma and pituitary concentrations of LH,FSH, and Prolactin in aging C57BL/6 mice at various times of the estrous cycle

—Plasma and pituitary concentrations of LH, FSH, and prolactin (Prl) were measured by RIA in 2–4, 7–8, 12–13 and 16–20 month-old female C57BL/6 mice during various stages of the estrous cycle. In general, gonadotropin concentrations tended to rise with increasing age and Prl concentrations tended to decline. Pronounced differences existed, however, between the four age groups around the time of the LH surge. LH secretion declined progressively with increasing age at 21.00 hr of proestrus. Aged mice, 16–20 months old, had significantly lower plasma concentrations of LH than did other age groups. It is not known whether age-related changes in the ovary, pituitary, or hypothalamus are largely responsible for differences in the secretion of LH, FSH and Prl in aging C57BL/6 mice.     

Cholinergic neurons in the pedunculopontine tegmental nucleus are involved in the mediation of prepulse inhibition of the acoustic startle response in the rat

The amplitude of the acoustic startle response (ASR) is markedly reduced when the startle eliciting pulse is preceded by a weak, non-startling stimulus at an appropriate lead time, usually about 100 ms. This phenomenon is termed prepulse inhibition (PPI) and has received considerable attention in recent years as a model of sensorimotor gating. We report here on experiments which were undertaken in order to investigate some of the neural mechanisms of PPI. We focused on the characterization of the cholinergic innervation of the pontine reticular nucleus, caudal part (PnC), an obligatory relay station in the primary startle pathway. The combination of retrograde tracing with choline acetyltransferase-immunocytochemistry revealed a cholinergic projection from the pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDTg) to the PnC. Extracellular recording from single PnC units, combined with microiontophoretic application of the acetylcholine (ACh) agonists acetyl--methylcholine (AMCH) and carbachol revealed that ACh inhibits the majority of acoustically responsive PnC neurons. Neurotoxic lesions of the cholinergic neurons of the PPTg significantly reduced PPI without affecting the ASR amplitude in the absence of prepulses. No effect on long-term habituation of the ASR was observed. The present data indicate that the pathway mediating PPI impinges upon the primary acoustic startle circuit through an inhibitory cholinergic projection from the PPTg to the PnC.     

Influence of individual differences in the Behavioral Inhibition System and stimulus content (fear versus blood-disgust) on affective startle reflex modulation

Inconsistencies among affective startle reflex modulation studies may be due to differences in the startle potentiation produced by the specific content of the images used, to individual differences in sensitivity to negative stimuli, or to the interaction of both factors. To explore this interaction, 52 undergraduates obtaining extreme scores on a self-report measure of the Behavioral Inhibition System (BIS) participated in an affective startle reflex modulation paradigm. A significant interaction between BIS group (high versus low) and image content emerged from the MANOVA. Comparing startle magnitude between fear and pleasant images, low BIS participants did not seem to show startle potentiation, whereas high BIS participants did. Both groups displayed potentiated startle during blood-disgust images. The present results suggest the importance of considering personality variables and their interaction with image content in the affective startle modulation paradigm.     

Time-specific action of N-methyl-N-nitrosourea in the occurrence of retinal dysplasia and retinal degeneration in neonatal mice

The morphologic response of neonatal mouse retina to the alkylating agent N -methyl- N -nitrosourea (MNU) was examined at different periods of retinal development. A dose of 60 mg/kg N -methyl- N -nitrosourea was injected intraperitoneally to neonatal C₅₇BL mice at 0, 3, 5, 8, 11, 14, 17, and 20 days of age and to C₃H mice at 0 days of age, and the retinas were examined sequentially. In the C₆₇BL mice, MNU evoked a time-dependent occurrence of retinal dysplasia and retinal degeneration. With MNU treatment at day 0 and day 3 (the stage of retinal cell proliferation), retinal dysplasia characterized by the progressive disorganization of neuroblasts, which led to the formation of rosettes, was found in the outer neuroblastic/nuclear layer above the normal pigment epithelial cells during days 8–20, but decreased at day 50. The rosettes were surrounded by photoreceptor segments and Muller cell processes, and by photoreceptor nuclei. The MNU response was related to retinal differentiation; following MNU treatment at day 5 or 8 (the stage of retinal cell differentiation) the cells were much less sensitive (i.e. no retinal response was found). However, with MNU treatment at days 11, 14, 17, and 20 (after cellular differentiation), retinal degeneration characterized by selective photoreceptor apoptosis was seen. These results suggest that there is a critical period for the time of MNU administration in the development of mouse retinal lesions. In C₃H ( rd/rd ) mice, MNU treatment at day 0 resulted in retinal degeneration with only slight rosette formation at the peripheral retina.     

Effect of testosterone and the oestrous cycle on neuronal refractory periods and firing rates of stria terminalis neurones in the female rat

Summary Absolute refractory periods of a subpopulation of corticomedial amygdala (CMA) neurones which project to the medial preoptic/ anterior hypothalamic junction (MPH) via the stria terminalis were recorded in the female rat. Previous experiments have shown that this sub-population of CMA neurones is testosterone-sensitive in the male rat. In the ovariectomised female testosterone propionate (TP, 200 g/day for 18–22 days) significantly reduced the mean absolute refractory period of these CMA neurones compared to oil treated controls (from 1.34 ms to 0.87 ms). In a second experiment the absolute refractory periods of these CMA neurones were measured during the pro-oestrus and di-oestrus stages of the oestrous cycle as well as in ovariectomised controls. The mean absolute refractory period of these neurones was significantly shortened at pro-oestrus (0.99 ms) compared both to animals in di-oestrus 1 (1.45 ms) and ovariectomised controls (1.42 ms). The median firing rate of these CMA neurones was also significantly increased at pro-oestrus (1.24 Hz) compared to di-oestrus 1 (0.13 Hz) and ovariectomised controls (0.09 Hz). No firing rate increase was observed after TP treatment of ovariectomised animals in the first experiment.Results show that the testosterone-sensitive CMA neurones originally discovered in the male rat have a similar sensitivity in the female rat. They also show that the refractory periods of these neurones are shortened at pro-oestrus. Further, these same neurones also show firing rate increases at this time, although such an increase has not been observed in gonadally intact male rats when compared to castrated ones. Results are interpreted in terms of a possible functional sexual dimorphism in the output of these CMA neurones.Supported by the Medical Research Council