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PubMed2006

Neonatal hippocampal Tat injections: developmental effects on prepulse inhibition (PPI) of the auditory startle response.

The current estimate of children (<15 years) living with HIV and AIDS is 2.2 million. The major source of infection occurs through vertical transmission of the virus from mother to child during delivery [UNAIDS/WHO, 2005. AIDS Epidemic Update. UNAIDS, Geneva]. Recent studies have shown that timing of HIV-1 infection might be related to the onset and rate of progression of CNS disease. The effects of HIV on the brain are thought to be mediated indirectly through the viral toxins Tat and gp120. This study characterized developmental effects on PPI following intrahippocampal administration of Tat. On postnatal day (P)1, one male and one female pup from each of eight Sprague-Dawley litters were bilaterally injected with 50 microg Tat or saline (1 microl volume). Animals were tested for PPI of the auditory startle response (ASR) (ISIs of 0, 8, 40, 80, 120, and 4000 ms, six trial blocks, Latin-square design) on days 30, 60 and 90. Tat altered PPI and the pattern of alterations was different for males and females. For males, a leftward shift was evident in the ISI for maximal inhibition of the response on day 30 and on day 60 (chi(2)(1)=4.7, p< or =.03, and chi(2)(1)=5.3, p< or =.02, respectively), but not on day 90. For females, Tat altered peak ASR latency across PPI trials (8-120 ms) at all days of testing (30, 60, and 90 days of age), as indexed by orthogonal component analyses, indicating less modulation of PPI by ISI. Data collected from a second group that were tested only once at 90 days of age, suggested that the observed adverse Tat effects for males and females early in development were maintained with age. Thus, the diminishing TAT effect on PPI at day 90 in a longitudinal study design was attributed to repeated testing, rather than 'recovery of function'. Collectively, the data suggested that hippocampal Tat injections in neonatal rats produced alterations in the pre-attentive process of sensorimotor gating, as indexed by PPI.

Acoustic Stimulation↗
PubMed1996

Prepulse effects on magnitude estimation of startle-eliciting stimuli and startle responses.

The present studies investigated the relationship between prepulse effects on the modification of the brainstem startle reflex and magnitude estimates of startle-eliciting stimuli. In Experiment 1, startle eyeblink responses were elicited in 24 students, half of whom were instructed to estimate the loudness of the startle stimulus (actual intensities of 80, 90, and 100 dB) and half of whom were instructed to estimate the magnitude of their eyeblink. When weak acoustic prepulses preceded the startle-eliciting stimulus, eyeblink amplitude was inhibited, and estimates of response magnitude decreased, but estimates of startle stimulus magnitude decreased only when 100-dB startle stimuli were presented. In Experiment 2, the same startle stimuli were preceded on some trials by a vibrotactile prepulse to the hand. In conditions in which startle amplitude was inhibited, startle stimulus magnitude estimates were not affected. This suggests that the effect of acoustic prepulses on 100-dB startle stimuli in Experiment 1 may have been due to loudness assimilation, an effect independent of the prepulse inhibition of startle responding.

Acoustic Stimulation↗
PubMed2005

Sex effects in prepulse inhibition and facilitation of the acoustic startle response: implications for pharmacological and treatment studies.

Prepulse inhibition (PPI) refers to the reduction in the response amplitude to a startling stimuli (pulse) if it is preceded (i.e. 30-500 ms) by a weak stimulus (prepulse). If the time interval between the prepulse and pulse is more than 500 ms, then an increase in this response amplitude can be seen, termed prepulse facilitation (PPF). PPI is thought to represent an operational index of sensorimotor function whereas PPF is thought to reflect, at least to some degree, sustained attention. Interestingly, PPI is found to be sexually dimorphic, with men exhibiting more PPI than women when subjects are tested without regard to where they are in the menstrual cycle, and to be impaired in several neuropsychiatric disorders known to exhibit sex differences in their clinical presentation. PPF has received relatively less attention in both normal and clinical studies. This study examined sex differences in both PPI and PPF in 62 healthy subjects (34 women, 28 men) using a range of prepulse-to-pulse intervals to elicit PPI (30, 60, 120, 240 and 480 ms) and PPF (1000 and 2000 ms). Men showed higher PPI than women but women showed higher PPF compared to men. These results suggest that reduced PPI in healthy women is not a simple reduction but rather a shift of the inhibition/facilitation curve in the direction of facilitation in women, relative to men. Future studies investigating pharmacological and treatment effects using a prepulse modification paradigm in normal and clinical populations of both sexes would benefit from an examination of sex effects and assessments of both PPI and PPF.

Acoustic Stimulation↗
PubMed1994

Modulation of the acoustic startle response by film-induced fear and sexual arousal.

The response matching model of Lang, Bradley, and Cuthbert (1992) predicts startle reflex facilitation during negative relative to positive emotional states. Using slide and imagery paradigms, larger eyeblink responses to startle probes for unpleasant than for pleasant conditions have consistently been reported. The present study extended the previously observed relationship between valence and startle to more complex stimuli, namely 1-min film fragments. Thirty-three subjects viewed a sequence of 27 film fragments with neutral, negative (fearful), and positive (sexual) contents, presented in one of three mixed orders. Blink magnitude to brief bursts of white noise was larger during fearful fragments than during sexual fragments. Blink magnitudes habituated across successive film fragments, but the positive-negative difference remained stable within film fragments and during the entire length of the videotape (approximately 40 min).

Acoustic Stimulation↗
PubMed2000

Purkinje cell degeneration and control mice: responses of single units in the dorsal cochlear nucleus and the acoustic startle response.

The cartwheel cell is the most numerous inhibitory interneuron of the dorsal cochlear nucleus (DCN). It is expected to be an important determinant of DCN function. To assess the contribution of the cartwheel cell, we examined the discharge characteristics of DCN neurons and behavioral measures in the Purkinje cell degeneration (pcd) mice, which lack cartwheel cells, and compared them to those of the control mice. Distortion product otoacoustic emissions and auditory brainstem-evoked response thresholds were similar between the two groups. Extracellularly recorded DCN single units in ketamine/xylazine-anesthetized mice were classified according to post-stimulus time histogram (PSTH) and excitatory-inhibitory response area (EI-area) schemes. PSTHs recorded in mouse DCN included chopper, pauser/buildup, onset, inhibited and nondescript types. EI-areas recorded included Types I, II, III, I/III, IV and V. There were no significant differences in the proportions of various unit types between the pcd and control mice. The pcd units had slightly lower thresholds to characteristic frequency tones; however, they had spontaneous rates, thresholds to noise, and maximum driven rates to noise that were similar to those of the control units. Pcd mice had smaller startle amplitudes, but startle latency, prepulse inhibition/augmentation and facilitation by a background tone were comparable between the two groups. From these results, we conclude that DCN function in response to relatively simple acoustic stimuli is minimally affected by the absence of the cartwheel cells. Future studies employing more complex and/or multimodal stimuli should help assess the role of the cartwheel cells.

Acoustic Stimulation↗
PubMed1987

The startle response and auditory temporal summation in neonates.

The present study assessed temporal summation of transient and sustained stimuli in the startle eyeblink response system in neonates during quiet sleep. Subjects received 100-dB(A), fast-rising broadband noise bursts of two types: (a) single stimuli varying in duration from 20 to 100 ms and (b) pairs of 3-ms bursts presented at interpulse intervals corresponding to the single-stimulus durations. In addition, a single 3-ms pulse was used as an anchor point for both stimulus types. For startle amplitude, single stimuli were more effective than were paired stimuli, but the temporal summation functions were similar for the two types of stimuli. Response amplitude increased as stimulus duration/interval increased to 50 ms, but not beyond. For startle probability, temporal summation was similar for single and paired stimuli at 20 ms. Pairs of pulses were equally effective at 20, 35, and 50 ms, beyond which the second pulse was not effective. Increasing the duration of single stimuli from 20 to 35 ms resulted in increased probability, illustrating a contribution of sustained summation beyond that of transient summation. Response latency was generally greater for paired than for single stimuli. The results suggest that temporal summation of brief stimuli is deficient in the neonate. These data were compared to adult data from an analogous study, and suggest that the transient system is immature in infants, and that this immaturity is expressed differently by startle amplitude, probability, and latency.

Acoustic Stimulation↗
PubMed2003

Startle response to short acoustic stimuli in rats.

The acoustic startle (ASR) is a transient motor response to an unexpected, intensive stimulus. The response is determined by stimulus parameters such as its intensity, rise time and duration. The dependence of the ASR on the stimulus duration is more complex than could be assumed from physical properties of acoustic pulse. This effect attracted the attention of few researchers. Some authors reported noticeable changes in the ASR amplitude only for very short (less than 4-6 ms) acoustic pulses. The systematic studies on the effect, however, have not been performed so far. The purpose of this study was to determine to what extent the ASR parameters are affected by the durations of the short stimulus. The amplitude of the acoustic startle reflex was assessed for a fixed tonal frequency (6.9 kHz), and for a variety of stimulus durations ranging between 2 and 10 ms. ASRs were studied in 11 adult, hooded rats exposed to a sequence of tone pulses (110 dB SPL) of different durations, presented in random order, with or without 70 dB white noise as a background. Statistical analysis revealed significant differences between ASR amplitudes for different durations. The startle amplitude increased with acoustic pulse duration and distinguishable differences were seen for stimulus duration between 2 and 8 ms. Further increase of pulse duration had no effect on ASR amplitude. The same pattern of changes was observed when the acoustic stimulus was presented with the white noise. In the tested range of stimulus duration no significant differences in the ASR latency were found. The observed differences may be attributed to changes of stimulus acoustic energy and to physiological characteristic of auditory system in the rat.

Acoustic Stimulation↗
PubMed1985

Evoked fetal startle response: a possible intrauterine neurological examination.

The fetal startle reflex was studied in an attempt to provide an objective and quantitative estimate of the fetal neurological condition. This reflex is a normal response to a combined sound-vibratory stimulus in the healthy infant born after 30 weeks of gestation. It consists of a generalized paroxysmal motion that involves the whole body. Thirty women with uncomplicated pregnancies, who subsequently delivered healthy infants, were studied at term. Fetal movements were monitored by means of a real-time scanner. Placement of the transducer was such that it allowed for visualization of the long axis of the fetal forearm. A 3-second stimulus was delivered on the maternal abdomen over the fetal head with use of an artificial larynx. This device generates a mixed sound-vibratory output of 100 dB and 85 Hz. Sufficient visualization of the plane of forearm motion was possible 68% of the time, thus allowing for measurement of the duration of this motion. The results indicate that the mean duration of forearm motion in response to a 3-second sound-vibratory stimulus is 8.2 +/- 2.3 seconds (+/- SEM). Since an immediate forearm motion was detected each time that a stimulus was applied, we conclude that the startle reflex does indeed exist in the fetus. This simple means of assessing the neurological state of the fetus may provide a way to evaluate fetal tone as it applies to antenatal fetal assessment.

Acoustic Stimulation↗
PubMed2000

Modulation of the startle response during human gait.

While many studies have shown that there is a phase-dependent modulation of proprioceptive and exteroceptive reflexes during gait, little is known about such modulation for auditory reflexes. To examine how startle reactions are incorporated in an ongoing gait pattern, unexpected auditory stimuli were presented to eight healthy subjects in six phases of the step cycle during walking on a treadmill at 4 km/h. For both legs, electromyographic activity (EMG) was recorded in the biceps femoris (BF), the rectus femoris (RF), the tibialis anterior (TA), and the soleus (SO). In addition, stance and swing phases of both legs, along with knee angles of both legs and the left ankle angle, were measured. All subjects showed various response peaks. Responses with latencies of approximately 60 ms (F1), approximately 85 ms (F2), and approximately 145 ms (F3) were found. The amplitude of the reflex responses was dependent on the timing of the startle stimulus in the step cycle. Although the startle response habituated rapidly, the phase-dependent modulation pattern generally remained the same. The phase-dependent amplitude modulations were not strictly correlated with the modulation of the background activity. The TA even showed a transition from facilitatory F2 responses during stance to suppressive responses during midswing. Responses were observed in both flexors and extensors, often in coactivation, especially during stance. Furthermore the gait characteristics showed a shortening of the subsequent step cycle and a small decrease in the range of motion of ankle and knees. These results suggest that the responses are adapted to achieve extra stability dependent on the phase of the step cycle. However, even in the first trials, the changes in kinematics were small allowing a smooth progression of gait.

Adult↗
PubMed2003

Deficient attentional modulation of the startle response in patients with schizotypal personality disorder.

OBJECTIVE: Attentional deficits have been identified as an abnormality that individuals with schizotypal personality disorder share with schizophrenia patients. The purpose of this study was to examine automatic sensorimotor gating and controlled attentional modulation of the startle eye blink response in unmedicated subjects with schizotypal personality disorder. METHOD: Eighteen unmedicated patients with schizotypal personality disorder and 16 healthy individuals were assessed in an acoustic attention-to-prepulse paradigm. The participants performed a selective attention task involving the presentation of attended, ignored, and novel tones that served as prepulse tones. Acoustic startle probes were presented at short and long lead intervals after the onset of tones and occasionally during the intertone interval. RESULTS: The comparison subjects showed greater prepulse inhibition and prepulse facilitation during the attended than the ignored prepulses, demonstrating early and later attentional modulation of startle eye blink response. In contrast, the subjects with schizotypal personality disorder failed to show this pattern. CONCLUSIONS: Subjects with schizotypal personality disorder have deficits in controlled attentional processing, as indexed by modification of the startle eye blink response, that are similar to those observed in patients with schizophrenia.

Acoustic Stimulation↗
PubMed1996

Inhibition of the human startle response is affected by both prepulse intensity and eliciting stimulus intensity.

The present study evaluated the effects of the intensity of prepulses and eliciting stimuli on the modification of the adult human acoustic startle eyeblink. Eyeblinks were elicited by 85, 95, and 105 dB(A) noise bursts, preceded a some trials by 60 or 70 dB(A) tones at a 120 ms stimulus onset asynchrony. Prepulse intensity was a within-subject variable in Experiment 1 (N = 19) and a between-groups variable in Experiment 2 (N = 38). For no-prepulse trials, as startle stimulus intensity decreased, startle amplitude, probability, and magnitude decreased, and startle latency increased. As startle stimulus intensity decreased from 105 to 95 dB, the amount of inhibition of response amplitude and magnitude remained stable for 70 dB prepulses in Experiment 1 and for both 60 and 70 dB prepulses in Experiment 2, whereas inhibition of response probability became more pronounced. As startle stimulus intensity decreased from 95 to 85 dB, prepulse inhibition of response amplitude and magnitude lessened and inhibition of response probability became still more pronounced in both experiments. These data show that the inhibition of startle can be affected by eliciting stimulus intensity, and that startle response amplitude and probability are affected by stimulus intensity changes in different ways.

Acoustic Stimulation↗
PubMed1982

Hyperexplexia: an inherited disorder of the startle response.

A family is presented with hyperexplexia, a rare autosomal dominant neurological disorder. Affected individuals manifest flexor hypertonia and hypokinesia during infancy. Later and throughout life, the condition is characterized by exaggerated involuntary myoclonic startle reactions, which on occasion result in falling. There are also marked nocturnal myoclonic jerks. Many family members have had congenital hip dislocations and inguinal hernias. Pre- and postnatal hypertonia is proposed as the cause for these problems. The nature and location of central nervous system dysfunction in hyperexplexia was investigated using electroencephalographic and brainstem-evoked response techniques. A dysfunction of cortical inhibition of the brainstem-mediated startle response is discussed as a possible pathogenic mechanism. Accurate diagnosis of this disorder is important in order to provide appropriate counseling and to initiate effective treatment.

Adolescent↗
PubMed1997

Auditory startle responses in help-seeking trauma survivors.

Studies of the acoustic startle reflex in post-traumatic stress disorder (PTSD) yielded controversial results, whilst PTSD patients consistently report exaggerated startle. Addressing methodological difficulties of previous studies, the authors investigated the eyeblink, skin conductance and heart rate responses to 15 consecutive 95-dB, 500-ms, 1000-Hz sudden tones in 58 consecutive referrals of unmedicated help-seeking trauma survivors (30 with PTSD and 28 without PTSD). PTSD patients had higher average eyeblink and skin conductance responses to the tones. Differences between reports of exaggerated startle in PTSD and negative experimental findings may be explained by specific experimental conditions, such as reduced environmental input, and by concurrent use of medication.

Adult↗
PubMed1975

Startle responses recorded in the leg of man.

The EMG pattern of startle reactions in the leg was studied in man using a 100 msec, 1 kc/sec squre wave tone burst of 114 dB as the auitory stimulus. At rest, 74 responses were recorded in the ankle flexor tibialis anterior (TA) and 23 in the ankle extensor gastrocnemius (G) with a significantly different mean latency of 151 and 123 msecrespectively. During tonic extension or flexion of the ankle, the EMG response in TA or G consisted in a burst of activity superimposed on the voluntary EMG at a latency of approximately 150 msec after the onset of the tone burst and followed, at 200 msec, by a period of EMG silence lasting close to 100 msec. Similar periods of silence also occurred as the sole EMG modulation in response to sound. Although predominant in flexors, startle reactions are significant in extensors during or after tonic ankle extension suggesting that audiospinal influences may be channelled to one or the other group depending on their functional state. The silent period of EMG following an excitatory startle or appearing on its own suggests an important inhibitory component in audiospinal mechanisms particularly related to startle since it had not been disclosed in a previous study of the modulation of the H-reflex by non-startling auditory stimulus. From the distribution and EMG pattern of startle, it is inferred that audiospinal influences may be meaningfully integrated through the reticulospinal system in sound guided behaviour.

Acoustic Stimulation↗
PubMed1984

Hyperekplexia: a syndrome of pathological startle responses.

We describe a family and three sporadic cases of startle disease, or hyperekplexia. Sudden unexpected noises caused the patients to fall rigidly, often injuring themselves but retaining consciousness. This unusual entity differs from startle epilepsy and cataplexy. Clonazepam proved ineffective in three patients. Valproic acid, 5-hydroxytryptophan, or piracetam markedly reduced the abnormal startle in three patients.

5-Hydroxytryptophan↗
PubMed1977

Plasticity of the acoustic startle response in the acutely decerebrate rat.

Plasticity of the acoustic startle reflex was measured in rats in which a complete transection between the forebrain and midbrain was made. During a period from 60 to 100 min after surgery, startle amplitude in the transected rats was relatively stable and comparable with that of the controls (which had been anesthetized with halothane and placed in a stereotaxic instrument). During this period the transection did not alter the temporal recovery process (with intervals of 2, 4, 8, or 16 sec) or auditory prepulse inhibition (with intervals of 25, 50, 100, 500, or 1,000 msec) or the normal reduction in startle caused by high levels of background noise. The transection did prevent the normal increase in startle caused by moderate levels of background noise and eliminated within-session habituation. The effect on habituation was particularly convincing since the curves of the transected and nontransected rats actually crossed. The results are discussed in terms of how the transection procedure can be used to evaluate various hypotheses about underlying mechanisms of startle plasticity.

Acoustic Stimulation↗
PubMed2006

Increased prepulse inhibition of the acoustic startle response is associated with better strategy formation and execution times in healthy males.

Prepulse inhibition (PPI) refers to the attenuation of the amplitude of the startle reflex in response to sudden intense stimuli (pulse) if preceded by a weaker sensory stimulus (prepulse). PPI reflects the ability to filter out irrelevant information in the early stages of processing so that attention can be directed to more salient environmental features. Inhibition at this early stage of information processing appears modulated by the prefrontal cortex in a "top-down" fashion and this may account for the normal inter-individual variability in PPI and in cognitive performance. PPI data were calculated from 82 healthy male subjects who were also tested in problem solving (Stockings of Cambridge; SoC), spatial working memory (SWM) and 5-choice reaction time (RT) tests from the Cambridge Neuropsychological Test Automated Battery. Correlations between PPI scores and cognitive test variables were examined. In addition PPI scores were divided in quartiles which were used as grouping factors in examining cognitive test performance. Compared to individuals in the lowest quartile those in the highest had (a) shorter execution but not reaction times on the 5-choice RT, (b) shorter subsequent but not initial thinking times in the SoC where they also solved more problems correctly with the minimum number of moves, and (c) better strategy but not errors scores in the SWM. Our findings suggest that greater PPI is associated with superior abilities in strategy formation and execution times. We suggest that this is due to more efficient early information processing.

Acoustic Stimulation↗
PubMed1995

Predictive validity of the potentiated startle response as a behavioral model for anxiolytic drugs.

The fear-potentiated startle (PSR) paradigm is a putative behavioral model for the determination of anxiolytic properties of drugs. The present study further investigated the predictive validity of the model. Predictive validity is high, when only drugs clinically used as anxiolytics attenuate PSR dose dependently. Results showed that startle potentiation decreased dose dependently after the administration of the anxiolytics CDP (2.5-10 mg/kg, IP) and alprazolam (1-3 mg/kg, IP). After administration of the clinically non-anxiolytic drugs amitriptyline (2.5-10 mg/kg, IP), carbamazepine (5-20 mg/kg, IP), fentanyl (0.0025-0.04 mg/kg, SC), naloxone (2.5-10 mg/kg, IP), nicotine (0.4-1.6 mg/kg, IP), alcohol (500-2000 mg/kg, IP), and d-amphetamine (0.6-2.4 mg/kg, IP), a dose-dependent decrease in startle potentiation was not found. The PSR correctly discriminated most of the drugs tested in clinically anxiolytic and clinically non-anxiolytic drugs. However, haloperidol behaved as a false positive, and results of nicotine and alcohol were at variance with results reported by others.

Alprazolam↗