Stimulus quality affects expression of the acoustic startle response and prepulse inhibition in mice

The relationship between stimulus intensity and startle response magnitude (SIRM) can assess the startle reflex and prepulse inhibition (PPI) with advantages over more commonly used methods. The current study used the SIRM relationships in mice to determine differences between white noise and pure tone (5 kHz) stimuli. Similarly to rats, the SIRM relationship showed a sigmoid pattern. The SIRM-derived reflex capacity (RMAX) and response efficacy (slope) of the white noise and pure tone stimuli in the absence of prepulses were equivalent. However, the pure tone startle response threshold (DMIN) was increased whereas the stimulus potency (1/ES50) was decreased when compared to white noise. Prepulses of both stimulus types inhibited RMAX and increased DMIN, but the white noise prepulses were more effective. Both stimulus intensity gating and motor capacity gating processes are shown to occur, dependent on prepulse intensity and stimulus onset asynchrony. Prepulse intensities greater than 10 dB below the startle threshold appear to produce PPI via stimulus intensity gating, whereas a motor capacity gating component appears at prepulse intensities near to the startle threshold.     

Tuning of the ocular vestibular evoked myogenic potential (oVEMP) to air- and bone-conducted sound stimulation in superior canal dehiscence

Recent studies have demonstrated the frequency selectivity of air-conducted (AC) and bone-conducted (BC) stimuli in eliciting ocular vestibular evoked myogenic potentials (oVEMPs). In this study, frequency tuning of the oVEMP was assessed in patients with superior canal dehiscence (SCD) and compared with responses previously reported for healthy subjects. Six (five unilateral) SCD patients were stimulated using AC sound (50–1,200 Hz) and BC transmastoid vibration (50–1,000 Hz). Stimuli were delivered at two standardized intensities: one the same as previously used for healthy controls and the other at 10 dB above vestibular threshold (a similar relative intensity to that used in controls). For AC stimulation, SCD patients had larger oVEMP amplitudes across all frequencies tested for both stimulus intensities. Normalized tuning curves demonstrated greater high-frequency responses with the stronger stimulus. For BC stimulation, larger oVEMP amplitudes were produced at frequencies at and above 100 Hz using standard intensity stimuli. For the matched intensity above vestibular threshold, enhancement of the oVEMP response was present in SCD patients for 500–800 Hz only. We conclude that SCD causes greater facilitation for AC than BC stimuli. The high-frequency response is likely to originate from the superior (anterior) canal and is consistent with models of inner ear changes occurring in SCD.     

Gating of the Auditory Evoked Potential in Children and Adults

Auditory evoked potentials were recorded from 163 subjects, aged IS months to 55 years. A conditioning-testing paradigm was used to assess sensory gating. In this paradigm, click stimuli are presented in pairs to the subjects with a 0.5-second intrapair interval. In normal adults, the first stimulus activates or “conditions” sensory gating mechanisms. The strength of these mechanisms is “tested” by the second stimulus, which produces a response whose amplitude is significantly suppressed. This aspect of sensory gating was not reliably observed in our subjects until age 18 years. Younger subjects varied widely in their ability to demonstrate sensory gating. Mean levels of suppression increased during late childhood and adolescence, with no relationship to other changes in evoked potential amplitude and latency. Sensory gating would appear to be a late developing aspect of human sensory physiology.     

Early rehabilitation outcome in patients with middle cerebral artery stroke

We aimed to evaluate the effect of arousal level in healthy subjects on P50 potential, as the variation in the level of arousal may be a source of variance in the recordings as well as it may provide additional information about the pathology under study. Eleven healthy volunteers participated in the study. A standard auditory P50 potential paradigm was applied. Two stimulation conditions were selected: eyes-open, i.e., high arousal level condition and eyes-closed, i.e., low arousal level condition. P50 component amplitudes in response to both the first (S1) and second stimulus (S2) of the pair, their ratio and difference were evaluated. P50 amplitude in response to S1 was significantly higher during the low arousal closed eyes condition as compared to high arousal open eyes condition. There was no P50 amplitude difference in response to S2 and no arousal effect on gating measures. This prompts for more careful evaluation of patients' arousal level when performing P50 studies and interpreting the results.     

Auditory brainstem responses in the aged cat

Auditory brainstem responses (ABRs) were compared in young adult and aged cats. Mean thresholds for click-evoked ABRs were greater in the aged cats. Clicks normalized to 15 and 30 dB above individual thresholds at rates of 10, 20, 50 and 100/sec evoked ABRs with similar latencies and central conduction times in both groups. Background noise at equal intensity for all cats completely suppressed ABRs evoked by clicks 30 dB above threshold in 2/3 of the young but none of the old cats. As rise time of a 25 msec noise burst at equal intensity for all cats increased 1, 2, 5, and 10 msec, latency of wave 4 increased more for the old cats than for the young. Summed monaural ABRs from both ears were greater than binaural ABRs for waves 4 and 5 in both groups. These data indicate peripheral auditory dysfunction in aged cats but little abnormality in auditory brainstem transmission with click intensity normalized for ABR threshold.     

Neuroanatomical and Physiological Foundations of Extraversion

Two auditory brainstem evoked potential studies were carried out to investigate the role of sensory influences, independent of factors such as attention and arousal, in groups varying in extraversion. In the first experiment, the rate of stimulus presentation was either 11, 41 or 81 clicks/sec, stimulus intensity being held constant at 70dB above the threshold of a normal young adult sample. Neither the latency nor the amplitude of any of the brainstem components significantly differed among the introverted, ambiverted or extraverted groups for any rate of presentation. In the second experiment, repetition rate was either 41 or 81 clicks/sec and intensity established at 20, 30, 50 and 70 dB. Peak V showed a highly consistent and significant increase in latency and decrease in amplitude with decreasing intensity. Again, however, no inter-group differences were found. The results suggest that N1-P2 effects that have been found at higher levels of the brain are probably not due to parallel changes in the periphery or the brainstem. The possibility that non-sensory factors, such as attention and motivation, might have accounted for these cortical differences is also discussed.     

Discharge properties of primary auditory fibres in caiman crocodilus: Comparisons and contrasts to the mammalian auditory nerve

Summary Single fibre recordings were performed from the auditory nerve of the caiman, Caiman crocodilus. All neurones were spontaneously active (1–80 imp/s). Clicks evoked multiple peaks in the post stimulus time histogram spaced at 1/CF. At high intensities irregularities were observed. The latencies of the first peak observable were intensity-dependent and related to CF. The number of peaks was correlated with tuning properties of the fibre.Frequency threshold curves were asymmetrical, with low frequency slopes less steep than high frequency slopes. Q₁₀ dB was between 1.5 and 7 with best tuning at high CF. CF ranged from 30 Hz to 2.8 kHz, lowest thresholds down to 5 dB SPL. Intensity functions were nonmonotonic.In isointensity contours the best frequency shifted downwards with increasing stimulus level. At highest levels a response dip was observed above CF.Phase locking, two tone suppression and excitability by combination tones were observed.In comparison to the mammalian cochlea similarities and differences were found.     

Multichannel electroencephalographic assessment of auditory evoked response suppression in schizophrenia

Reduced auditory evoked response (AER) suppression in a paired-stimulus paradigm (where suppression equals the difference between S1 and S2 amplitudes divided by S1 amplitude) may index genetic liability for schizophrenia. The present report is a multiple-channel electroencephalographic (EEG) study of AER suppression among 20 normal and 20 schizophrenia subjects. The typical paired-stimulus paradigm was used to evoke time-locked AERs. AER responses were scored at P50 and N100 in the time domain using both single (Cz) and multichannel data (after reduction using principal components analysis, PCA), and were scored for information in the gamma (20–50 Hz) and low-frequency (1–20 Hz) ranges using multichannel information (also after PCA). The time domain analyses demonstrated that schizophrenia patients differ from normal in amplitude of response to the first, but not to the second, stimulus for both P50 and N100. The frequency domain data demonstrated that schizophrenia patients differed from normal on amplitude of the low-frequency response (LFR) to the first, but not to the second, stimulus. The groups did not differ significantly on amplitudes of the gamma-band responses. Group separations were largest for the multichannel N100 and LFR data, with the LFR demonstrating a modestly better risk ratio for differentiating schizophrenia from normal subjects. The present results suggest two novel differences from previous AER suppression studies: (1) S1 amplitudes largely determine differences between normal and schizophrenia groups on AER suppression, and (2) frequency domain analyses may provide important complimentary information when studying AERs in schizophrenia. Electronic Publication     

Modification of the Acoustic Startle Reflex by a Tactile Prepulse: The Effects of Stimulus Onset Asynchrony and Prepulse Intensity

The present experiments were designed to assess the effects of a tactile prepulse on the acoustic startle response in human adults. Acoustic startle stimuli were presented via loudspeaker, and tactile prepulse stimuli were presented by a vibrator contactor on the thenar eminence of the right band. In Experiment 1 stimulus intensity was 20dB above each individual subject's psychophysical tactile threshold and stimulus onset asynchrony (lead time) was 50, 100, 200. or 300 ms, with a control condition in which no prepulse was presented. In Experiment 2, the same stimuli were used, except that tactile prepulse intensity was varied (?4, 0, 4, 8, 12, and 20 dB above each subject's psychophysical threshold), and lead time was constant at 200 ms. Reflex eyeblink responses were assessed from integrated periorbital etectromyographic (EMG) activity. Compared to responding in the control condition (no prepulse), a prepulse at a 50-ms lead time facilitated responding by increasing response amplitude and decreasing latency. At a lead time of 100 ms, the amplitude increase was no longer found, but the latency decrease was still apparent, as was a decrease in response probability. At lead times of 200 and 300 ms, responding was inhibited, as shown by-decreased response amplitude and probability. At a lead time of 200 ms. tactile prepulses as low as 8dB above threshold caused a reduction in response amplitude, but no effects of prepulse intensity on response probability or latency were found. The prepulse intensity and lead time effects shown in the present study demonstrate that the presentation of a brief, near-threshold tactile prepulse can either facilitate or inhibit an acoustically-elicited startle response, depending upon the temporal relationship between the two stimuli. Also, the different measures of the startle response reflect this modification in different ways.     

Orienting in Schizophrenia: Habituation to Auditory Stimuli of Constant and Varying Intensity in Patients High and Low in Skin Conductance Responsivity

Groups of schizophrenics and normal controls were exposed to different series of tones of constant (80dB) and variable intensity (60, 80, and 100 dB). Measurements included bilateral skin conductance, finger pulse volume, and heart rate. Both groups were split on the common median in skin conductance response to constant intensity tones to form matched patient and control groups of low and high responsivity. The low and high responsive schizophrenic groups were more clearly separated than the two control groups in rate of spontaneous skin conductance fluctuations, skin conductance magnitudes, and skin conductance levels, primarily because of generalized hyperactivity in high responsive patients. This pattern was clearest for the most intense tone and left hand recordings. High responsive schizophrenics also showed larger response amplitudes, shorter rise and recovery times, and a smaller ratio of elicited to spontaneous responses, than high responsive controls. Finger pulse volume responses recorded from the left hand were smaller in the patient groups, whereas patients and controls did not differ in right hand recordings. High skin conductance responsive subjects showed more heart rate deceleration than low responsive subjects, and schizophrenics had more decelerative responses than controls.     

Comparison of sensory gating to mismatch negativity and self-reported perceptual phenomena in healthy adults

To better understand the possible functional significance of electrophysiological sensory gating measures, response suppression of midlatency auditory event related potential (ERP) components was compared to the mismatch negativity (MMN) and to self-rated indices of stimulus filtering and passive attention-switching phenomena in an age-restricted sample of healthy adults. P1 sensory gating, measured during a paired-click paradigm, was correlated with MMN amplitude, measured during an acoustic oddball paradigm (intensity deviation). Also, individuals that exhibited less robust P1 suppression endorsed higher rates of "perceptual modulation" difficulties, whereas component N1 suppression was more closely related to "over-inclusion" of irrelevant sounds into the focus of attention. These findings suggest that the ERP components investigated are not redundant, but correspond to distinct-possibly related-pre-attentive processing systems.     

Single-unit responses in the inferior colliculus: different consequences of contralateral and ipsilateral auditory stimulation

Monaural excitatory responses of 181 single units in the central nucleus of the inferior colliculus of 15 anesthetized gerbils (Meriones unguiculatus) were examined quantitatively. Pure-tone stimuli were presented monaurally through sealed, calibrated sound-delivery systems. Most units were excited only by contralateral stimulation (EO); 23% were bilaterally excitable (EE). The threshold frequency tuning curves for contralateral stimulation of EE units were significantly broader than those produced by ipsilateral stimulation of EE units and those produced by contralateral stimulation of EO units. The frequency at which threshold was lowest (best frequency), or BF) was very similar for ipsilateral and contralateral stimulation of individual EE units; however, ipsilateral BFs were slightly but significantly lower than contralateral BFs. For EE units, ipsilateral BF thresholds (mean: 29.2 dB SPL) were significantly higher than contralateral BF thresholds (mean: 14.9 dB SPL). Monotonic and nonmonotonic relationships between discharge rate and stimulus intensity at BF were observed in responses evoked both by contralateral and ipsilateral stimulation. Interestingly, for individual EE units it was not uncommon for the rate/intensity function for one monaural condition to be monotonic although the relationship for stimulation of the other ear was markedly nonmonotonic. There was no qualitative difference between rate/intensity functions evoked by contralateral stimulation in EO and EE units. Ipsilateral discharge rates were characteristically much lower than contralateral rates for a given stimulus intensity. For 50 BF tones of 100 ms duration, the median peak numbers of discharges for contralateral stimulation of EO and EE units were 361 and 339, respectively; the median for ipsilateral stimulation of EE units was 102. The dynamic range of each rate/intensity function was calculated by measuring the intensity range associated with an increase in spike count from 10 to 90% of the peak rate. No differences were detected between the distributions of dynamic range for contralateral stimulation in EO or EE units, or between contralateral and ipsilateral dynamic ranges within individual EE units. For all response types the distributions of dynamic range were approximately normal, with means near 20 dB. The minimum mean latency to the first spike at BF was generally longer for ipsilateral than for contralateral responses.(ABSTRACT TRUNCATED AT 400 WORDS)     

Time course and magnitude of movement-related gating of tactile detection in humans. II. Effects of stimulus intensity

This study examined the effect of systematically varying stimulus intensity on the time course and magnitude of movement-related gating of tactile detection and scaling in 17 human subjects trained to perform a rapid abduction of the right index finger (D2) in response to a visual cue. Electrical stimulation was delivered to D2 at five different intensities. At the lowest intensity, approximately 90% of stimuli were detected at rest (1 x P(90)); four multiples of this intensity were also tested (1.25, 1.5, 1.75, and 2. 0 x P(90)). At all intensities of stimulation, detection of stimuli applied to the moving digit was diminished significantly and in a time-dependent manner, with peak decreases occurring within +/-12 ms of the onset of electromyographic activity in the first dorsal interosseous (25-45 ms before movement onset). Reductions in the proportion of stimuli detected were greatest at the lowest stimulus intensity and progressively smaller at higher intensities. No shift in the timing of the decreases in performance was seen with increasing intensity. Once the weakest intensity at which most stimuli were perceived during movement had been established (2 x P(90)), magnitude estimation experiments were performed using two stimulus intensities, 2 x P(90) (5 subjects) and 3 x P(90) (3 subjects). Significant movement-related decreases in estimated stimulus magnitude were observed at both intensities, the time course of which was similar to the time course of reductions in detection performance. As stimulus intensity increased, the magnitude of the movement-related decrease in scaling diminished. A model of detection performance that accurately described the effect of stimulus intensity and timing on movement-related reductions in detection was created. This model was then combined with a previous model that described the effects of stimulus localization and timing to predict detection performance at a given stimulation site, intensity, and time during movement. Movement-related gating of tactile perception represents the end result of movement-related effects on the transmission and subsequent processing of the stimulus. The combined model clearly defines many of the requirements that proposed physiological mechanisms of movement-related gating will have to fulfill.     

Extraversion and Individual Differences in Auditory Evoked Response

The auditory evoked response to low (0.5K Hz) and high (8.0K Hz) frequency tones at three levels of intensity (40, 55, and 80 dB) were recorded for subjects differing in degree of extra-version. Introverts were observed to have greater N₁-P₂ amplitude than extraverts with the low frequency tones at 55 and 80 dB intensity. The results support Eysenck's general proposal relating introversion to higher levels of cortical activity.     

Effects of intensity of repetitive acoustic stimuli on neural adaptation in the ventral cochlear nucleus of the rat

To study neural adaptation as a function of stimulus intensity, auditory near-field evoked potentials were recorded from the ventral cochlear nucleus in awake Long Evans rats. Responses to 250-ms trains of repetitive clicks (pulse rates ranging from 100 to 1000 pulses per second) were collected at stimulus intensities of 5, 10, 30, 50 and 70 dB SPL. The amplitude of the first negative (N₁) component of the average evoked potentials to individual pulses in the train was measured by using a subtraction method. The N₁ responses were normalized with respect to the highest cochlear nucleus potential observed in the train, and then plotted as a function of click position in the train. As expected, the general trend of the curves was an exponential decay reaching a plateau more or less rapidly as a function of both intensity and rate of stimulation. Fitting these curves with exponential decay equations revealed that the rapid time constant decreased for increasing stimulus intensities whereas the short-term time constant is relatively independent of intensity. The amount of adaptation (expressed as the ratio of the plateau to the first peak amplitude) was substantially less prominent at low intensities (5–10 dB SPL) and low rates (100–200 pulses per second) than at higher intensities and high rates. These results indicate that adaptation patterns obtained in the ventral cochlear nucleus by using near-field evoked potentials exhibit properties comparable to those already present at the level of the auditory nerve.     

Range of sensory gating values and test-retest reliability in normal subjects

This article characterizes gating in normal subjects using P50, N100, and P200 components in a paired-click paradigm and compares the test-retest reliabilities of the three components. Sixty-seven normal subjects had gating data from a standard paired-click paradigm; 30 had test-retest data. The test-retest reliability of the amplitudes, latencies, and sensory gating indices derived from the P50, N100, and P200 responses were compared. Measured gating ratios showed either normal or positively skewed distributions. Test-retest reliability of the P50 gating ratio did not reach significance, but N100 and P200 ratios showed better reliability (.50 and .64). The P50 difference score was more reliable (.61), and the N100 and P200 test-retest reliabilities of difference scores were high (.83 and .81, respectively). N100 and P200 attenuation is reliable; further work is needed to develop more reliable P50 gating measures.     

Effects of prepulse intensity, duration, and bandwidth on perceived intensity of startling acoustic stimuli

Intense abrupt stimuli can elicit a startle reflex; a weak "prepulse" 30-300 ms earlier can reduce both startle and perceived stimulus intensity. Prepulse inhibition (PPI) of startle, an operational measure of sensorimotor gating, is used to understand brain disorders characterized by gating deficits. Compared to startle, PPI of perceived stimulus intensity (PPIPSI) may provide information that is distinct, and easier to acquire and analyze. To develop this experimental measure, we examined PPIPSI under different stimulus conditions. Both PPI and PPIPSI exhibited a non-linear relationship to prepulse intensity, with prepulses 15 dB(A) above background causing maximal inhibition of both measures. A 50 ms broadband noise prepulse produced maximal PPI and PPIPSI, whereas 5 and 20 ms pure tone prepulses produced maximal PPIPSI and PPI, respectively. PPIPSI is a robust, parametrically sensitive and "low tech" measure of sensory gating that may become a valuable tool for understanding the biology of certain mental disorders.     

Parametric manipulations of auditory stimuli differentially affect P3 amplitude in schizophrenics and controls

Schizophrenics show P3 amplitude reduction and topographic asymmetries. It is unclear whether the underlying cause of these deficits is primarily functional or structural. This study examined the effect of stimulus discrimi-nability and task instruction on behavioral performance and P3 in schizophrenics and normal control subjects. Stimulus discriminability was manipulated by varying the overall loudness and pitch disparity of the two tones in an auditory oddball paradigm. Instructions emphasized either speed or accuracy of response. Instructions had no significant effects on reaction time, perceptual sensitivity, response bias, or P3. With increased discriminability, however, both groups improved in mean reaction time to targets and perceptual sensitivity. In controls, P3 became earlier and larger with increased stimulus discriminability and was consistently larger over left temporal areas than over right temporal areas. In schizophrenics, P3 latency was related to stimulus discriminability, but amplitude was not; P3 amplitude did not increase with improvement of perceptual sensitivity and reaction time. Unlike normal controls, schizophrenics had a P3 asymmetry at temporal sites, with reduced left-sided voltages. The results are not consistent with a primarily functional cause of P3 aberrations in schizophrenia and are compatible with the hypothesis that P3 amplitude deficits in schizophrenia are related to underlying pathophysiology of temporal lobe generator sites.     

Altered balance in the autonomic nervous system in schizophrenic patients

The aim of the present study was to evaluate the autonomic nervous function in schizophrenic patients. Twenty-eight patients (29 +/- 6 years) diagnosed as schizophrenics and in stable medication were included, together with ten schizophrenic patients (25 +/- 5 years) who were unmedicated. Eleven healthy subjects (32 +/- 7 years) served as controls. Immediate heart-rate responses to a single deep inspiration was used as a measure of parasympathetic function. Heart-rate response to standing was used as a measure of sympathetic function. Supine blood pressure, heart-rate and orthostatic changes in blood pressure did not differ between groups. Heart-rate response to standing was greater in both medicated and non-medicated schizophrenics compared to normal subjects (P less than 0.01). Heart-rate response to standing was greater in non-medicated compared to medicated schizophrenics (P less than 0.05). Heart-rate response to inspiration was greater in non-medicated schizophrenics compared to normal subjects (P less than 0.05), whereas no difference was found between medicated and non-medicated schizophrenics. The results show that the balance in the autonomic nervous system is altered in schizophrenic patients with a hyperexcitability in both the sympathetic and the parasympathetic division. Our study has thus indicated a dysfunction in the autonomic nervous system per se and the previous interpretations of attentional orienting responses in schizophrenia is questioned. Medication with neuroleptics seems to partly normalize the autonomic reactivity rather than being the cause of autonomic dysfunction.     

Lead stimulation effects on reflex blink, exogenous brain potentials, and loudness judgments

Prepulse inhibition of the reflex blink by a weak stimulus shortly preceding a blink-eliciting stimulus has been described as a sensorimotor gating phenomenon that may protect processing of the first stimulus. To determine how a stimulus configuration that elicits prepulse inhibition also affects exogenous evoked potentials and perceived loudness of the paired stimuli, the three types of response were recorded simultaneously under four conditions: tone pairs of 75–110 dB and 75–75 dB and single control tones of each intensity. Two studies using different intrapair intervals found that blinks and exogenous potentials peaking after 50 ms were smaller for the second tone of pairs than for equal-intensity single tones. Pairing also reduced the loudness of 110-dB second tones, but the loudness of 75-dB first and second tones was unaffected or increased. These effects are discussed in terms of parallel processing of transient, unmodulated information in specific paths, steady-state modulated information in nonspecific paths, and a context-dependent effect on loudness judgments.