Conditioning-testing Paradigm Research Articles

Sensory Gating in the Auditory System: Classical and Novel Stimulus Paradigms.

Sensory gating is a phenomenon where the cortical response to the second stimulus in a pair of identical stimuli is inhibited. It is most often assessed in a conditioning-testing paradigm. Both active and passive neuronal mechanisms have been implicated in sensory gating. The present study aimed to assess if sensory gating is caused by an active neural mechanism associated with stimulus redundancy. The study was carried out on 20 young neurotypical adults. We assessed the gating phenomenon using identical and nonidentical stimuli pairs presented in an electrophysiological conditioning-testing paradigm. We hypothesized that the novel stimulus in the nonidentical stimulus pair would not exhibit the sensory gating effects (reduction in the amplitude of cortical potentials to the second stimuli in the pair), owing to stimulus novelty. Contrary to our expectations, the response analyses of the cortical auditory evoked potentials revealed that adults gated repetitive and novel stimuli similarly. The findings are discussed in relation to the significance of methodological factors in evaluating sensory gating. We believe that additional research using oddball presentation of novel stimuli along with appropriate analysis methods is necessary before drawing any conclusions on the mechanisms underlying sensory gating.

Principal component analysis of auditory ERPs discriminates mild cognitive impairment and Alzheimer’s disease from normal aging

AbstractBackgroundSensory gating refers to an inhibitory mechanism of the brain that protects higher cortical centers from being flooded with repetitive, redundant sensory inputs. Sensory gating is modulated by cholinergic transmission, the deterioration of which is a prominent neurochemical feature of Alzheimer’s disease (AD), the most common form of dementia in the elderly. The study investigated whether alterations in inhibitory gating, assessed by event‐related potentials (ERPs) in response to repeated auditory stimuli, can discriminate AD and mild cognitive impairment (MCI) from normal aging.MethodEvent‐related electroencephalogram was recorded from 38 AD patients, 37 MCI patients, and 38 elderly cognitively normal control (NC) participants in a conditioning–testing paradigm. ERP waveforms, stimulus‐locked changes in power, and inter‐trial phase clustering (ITPC) were extracted and submitted to a covariance‐based principal component analysis (PCA) to yield data‐driven component measures.ResultNon‐parametric cluster‐based permutation tests revealed statistically significant differences for ERP waveforms in separating AD, for power in separating AD and MCI, and for ITPC in separating AD, MCI, and NC from the other two groups pooled together.ConclusionThe study confirms that alterations in auditory sensory gating can discriminate between AD, MCI, and normal aging. Auditory ERPs might serve as an objective, non‐invasive, and cost‐effective method for evaluating cognitive decline suggestive of AD and to monitor disease progression, therapeutic efficacy, or effects of novel drug candidates in clinical trials.

Combining CDP-choline and galantamine: Effects of a selective α7 nicotinic acetylcholine receptor agonist strategy on P50 sensory gating of speech sounds in healthy volunteers.

Schizophrenia (SCZ) patients and relatives have deficits in early cortical sensory gating (SG) typically measured by suppression of electroencephalography-derived P50 event-related potentials (ERPs) in a conditioning-testing (S1-S2) paradigm. Associated with alpha 7 nicotinic acetylcholine receptor (α7 nAChR) dysfunction and shown to be improved with nicotine and α7 nAChR agonists, SG has recently been shown to be improved in low P50 suppressing SCZ patients following acute CDP-choline treatment. This pilot study in healthy humans assessed the SG effects of an α7 nAChR strategy combining CDP-choline with galantamine, a positive allosteric modulator (PAM) of nAChRs, aimed at increasing and prolonging nicotinic receptor activity. The combined effect of CDP-choline (500 mg) and galantamine (16 mg) on speech P50 gating indices rP50 (S2/S1) and dP50 (S1-S2) was examined in 30 healthy participants stratified into low and high baseline P50 suppressors in a randomized, double-blind, placebo-controlled and counterbalanced design. In low suppressors, CDP-choline/galantamine (vs. placebo) improved rP50 and dP50 gating, and reduced S2P50 amplitudes. No P50 gating effects were observed in high suppressors; however, CDP-choline/galantamine (vs. placebo) increased their S2P50 amplitudes. Findings from this pilot study with CDP-choline/galantamine in a healthy, SCZ-like surrogate deficient gating sample are consistent with the association of α7 nAChR mechanisms in SG impairment in SCZ and support further research trials with CDP-choline and galantamine targeting sensory processes.

Combining CDP-choline and galantamine, an optimized α7 nicotinic strategy, to ameliorate sensory gating to speech stimuli in schizophrenia

Neural α7 nicotinic acetylcholine receptor (nAChR) expression and functioning deficits have been extensively associated with cognitive and early sensory gating (SG) impairments in schizophrenia (SCZ) patients and their relatives. SG, the suppression of irrelevant and redundant stimuli, is measured in a conditioning-testing (S1-S2) paradigm eliciting electroencephalography-derived P50 event-related potentials (ERPs), the S2 amplitudes of which are typically suppressed relative to S1. Despite extensive reports of nicotine-related improvements and several decades of research, an efficient nicotinic treatment has yet to be approved for SCZ. Following reports of SG improvements in low P50 suppressing SCZ patients and healthy participants with the α7 agonist, CDP-choline, this pilot study examined the combined modulatory effect of CDP-choline (500 mg) and galantamine (16 mg), a nAChR positive allosteric modulator and acetylcholinesterase inhibitor, on SG to speech stimuli in twenty-four SCZ patients in a randomized, double-blind and placebo-controlled design. As expected, in low P50 suppressors CDP-choline/galantamine (vs. Placebo) improved rP50 and dP50 scores by increasing inhibitory mechanisms as reflected by S2P50 amplitude reductions. Results also suggest a moderating role for auditory verbal hallucinations in treatment response. These preliminary findings provide supportive evidence for the involvement of α7 nAChR activity in speech gating in SCZ and support additional trials, examining different dose combinations and repeated doses of this optimized and personalized targeted α7 cholinergic treatment for SG dysfunction in subgroups of SCZ patients.

Optimal digital filters for analyzing the mid-latency auditory P50 event-related potential in patients with Alzheimer’s disease

BackgroundFiltering is an effective pre-processing technique for improving the signal-to-noise ratio of ERP waveforms. Filters can, however, introduce substantial distortions into the time-domain representations of ERP waveforms. Inappropriate filter parameters may lead to the presence of statistically significant but artificial effects, whereas true effects may appear as insignificant. New methodThe present study aimed to determine the optimal digital filters for analyzing the auditory P50 component in patients with Alzheimer’s disease. To provide evidence of the optimal filter settings, different high-pass and low-pass filters were applied to ERP waveforms obtained from a conditioning-testing paradigm. The results facilitate practical recommendations for selection of filters that maximize the signal-to-noise ratio of the P50 components without introducing significant distortions. ResultsThe present study confirms that filter parameters have a significant effect on the amplitude and gating measures of the P50 component. Setting the high-pass cut-off at 0.1Hz and the low-pass cut-off at 90Hz (or above) is recommended for P50 component analyses. Comparison with existing methodsThe majority of ERP studies on sensory gating report using high-pass filters with 10-Hz cut-offs to measure P50 suppression. Such a high cut-off appeared to induce significant distortions into the ERP waveforms; thus, the authors advise against using these excessive high-pass cut-offs. ConclusionsFiltering broadband signals, such as ERP signals, necessary results in time-domain distortions. However, by adjusting the filter parameters carefully according to the components of interest, it is possible to minimize filter artifacts and obtain more easily interpretable ERP waveforms.

Sensory Gating Capacity and Attentional Function in Adults With ADHD: A Preliminary Neurophysiological and Neuropsychological Study

Objective: The inability to filter sensory input correctly may impair higher cognitive function in ADHD. However, this relationship remains largely elusive. The objectives of the present study is to investigate the relationship between sensory input processing and cognitive function in adult patients with ADHD. Method: This study investigated the relationship between deficit in sensory gating capacity (P50 amplitude changes in a double-click conditioning-testing paradigm and perceptual abnormalities related to sensory gating deficit with the Sensory Gating Inventory [SGI]) and attentional and executive function (P300 amplitude in an oddball paradigm and attentional and executive performances with a neuropsychological test) in 24 adult patients with ADHD. Results: The lower the sensory gating capacity of the brain and the higher the distractibility related to sensory gating inability that the patients reported, the lower the P300 amplitude. Conclusion: The capacity of the brain to gate the response to irrelevant incoming sensory input may be a fundamental protective mechanism that prevents the flooding of higher brain structures with irrelevant information in adult patients with ADHD.

State-dependent changes in auditory sensory gating in different cortical areas in rats.

Sensory gating is a process in which the brain’s response to a repetitive stimulus is attenuated; it is thought to contribute to information processing by enabling organisms to filter extraneous sensory inputs from the environment. To date, sensory gating has typically been used to determine whether brain function is impaired, such as in individuals with schizophrenia or addiction. In healthy subjects, sensory gating is sensitive to a subject’s behavioral state, such as acute stress and attention. The cortical response to sensory stimulation significantly decreases during sleep; however, information processing continues throughout sleep, and an auditory evoked potential (AEP) can be elicited by sound. It is not known whether sensory gating changes during sleep. Sleep is a non-uniform process in the whole brain with regional differences in neural activities. Thus, another question arises concerning whether sensory gating changes are uniform in different brain areas from waking to sleep. To address these questions, we used the sound stimuli of a Conditioning-testing paradigm to examine sensory gating during waking, rapid eye movement (REM) sleep and Non-REM (NREM) sleep in different cortical areas in rats. We demonstrated the following: 1. Auditory sensory gating was affected by vigilant states in the frontal and parietal areas but not in the occipital areas. 2. Auditory sensory gating decreased in NREM sleep but not REM sleep from waking in the frontal and parietal areas. 3. The decreased sensory gating in the frontal and parietal areas during NREM sleep was the result of a significant increase in the test sound amplitude.

Acute administration of Δ9 tetrahydrocannabinol does not prevent enhancement of sensory gating by clozapine in DBA/2 mice

Despite high rates of marijuana abuse in schizophrenia, the physiological interactions between tetrahydrocannabinol (THC) and antipsychotic medications are poorly understood. A well-characterized feature of schizophrenia is poor gating of the P50 auditory-evoked potential. This feature has been translationally modeled by the DBA/2 mouse, which exhibits poor suppression of the P20–N40 AEP, the rodent analog of the human P50. Previous work has demonstrated that this deficit is reversed by the antipsychotic clozapine. It is unknown, however, if this effect is altered by THC administration. Using a conditioning–testing paradigm with paired auditory stimuli, the effects of clozapine and dronabinol (a pharmaceutical THC formulation) on inhibitory P20–N40 AEP processing were assessed from in vivo hippocampal CA3 recordings in anesthetized DBA/2 mice. The effects of clozapine (0.33mg/kg) and dronabinol (10mg/kg) were assessed alone and in combination (0.33, 1 or 1.83mg/kg clozapine with 10mg/kg dronabinol). Improved P20–N40 AEP gating was observed after acute administration of 0.33mg/kg clozapine. Co-injection of 0.33mg/kg clozapine and 10mg/kg THC, however, did not improve gating relative to baseline. This effect was overcome by higher doses of clozapine (1 and 1.83mg/kg), as these doses improved gating relative to baseline in the presence of 10mg/kg THC. 10mg/kg THC alone did not affect gating. In conclusion, THC does not prevent improvement of P20–N40 gating by clozapine.

Auditory Evoked Potential P50 as a Predictor of Neurologic Outcome in Resuscitated Cardiac Arrest Patients

In general, a prediction of neurologic outcome with respect to the resuscitated cardiac arrest patients has been performed by the auditory brainstem response and somatic evoked potential. The auditory brainstem response and somatic evoked potential are known as the predictors that correspond to neurologically poor outcome. None of the methods have been established to access neurologically good outcome. Because the hippocampal CA3 pyramidal cells have been widely used for pathophysiologic analyses concerning the hypoxic-ischemic encephalopathy and also the source of P50 components of the auditory evoked potential has been considered to be the hippocampal CA3 pyramidal cells, the authors assume that it might be possible that neurologic outcome in resuscitated cardiac arrest patients would be predicted by evaluating the P50 components. The purpose was to examine the P50 as a predictor of neurologic outcome in resuscitated cardiac arrest patients at the early stage from the onset. The P50 components of the auditory evoked potential are recorded in a conditioning-testing paradigm, that is, EEG responses to a pair of auditory stimuli with 500-millisecond interclick interval. In this study, subjects are 10 out-of-hospital cardiac arrest patients, 8 men and 2 women with a mean age of 54.8 years, who were admitted to the intensive care unit after the return of spontaneous circulation, with the presence of both the auditory brainstem response wave V and the somatic evoked potential wave N20 between the period from June 2008 to July 2009. It was found that the presence of the P50 at the early stage from the onset (days 5 ± 1.20) indicates good neurologic outcome, while the absence of the P50 implies poor prognosis. As to the auditory sensory gating of the P50, almost no reduction response to the second stimulus was observed. As a consequence, the evaluation of the P50 in resuscitated cardiac arrest patients would have a possibility to predict neurologically good outcome.

Timbre change detection reflected by auditory evoked responses

Event Abstract Back to Event Timbre change detection reflected by auditory evoked responses Jaeho Seol1*, June S. Kim2 and Chun K. Chung2 1 Seoul National University, Interdisciplinary Programs in Cognitive Science, College of Humanities, South Korea 2 Seoul National University College of Medicine, MEG Center, Department of Neurosurgery, South Korea Distinguishing the timbre differences is essential to the auditory processing including human cognition such as language or music. The purpose of this study was to reveal how and when human brain detects the timbre change based on the acoustic phase modulation by sensory gating [1]. Four different frequencies (262, 523, 1047 and 2093 Hz, which corresponds to C4, C5, C6 and C7 in musical key, respectively, with a length of 50 ms, were combined into a mixture tone, with two different phases; 0 and π. Two different or same tones are presented through a conditioning-testing paradigm as a pair with an interval of 500 ms.Fourteen normal subjects participated. Subjects were instructed to discriminate whether two tones in a pair are identical or different during magnetoencephalography recording using a 306 channel whole head MEG system (Elekta NeuroMag VectorView). Auditory responses are identified as M50 and M100 equivalent current dipoles for two tones in a pair for all conditions. Gating is assessed by the comparison of auditory responses between the first (S1) and second (S2) stimulus in a pair, whereas physical discrimination is assessed by the S1 comparison among conditions. Both M50 and M100 magnitudes were different in terms of order (S1 vs. S2) in both same and different condition on the left hemisphere, which might reflect the gating out effect. On the right hemisphere, M50 responses of S1 were different from those of S2 only in the different conditions, which suggest the timbre change detection. These results might suggest the lateralization of the inhibitory process explained by gating effect and timbre detection process [2].

Auditory sensory gating to the human voice: A preliminary MEG study

The ability of the brain to suppress incoming irrelevant sensory input is termed ‘sensory gating,' and auditory sensory gating is often indexed by the auditory evoked response. We recorded the auditory evoked magnetic fields to the human voice, using the conditioning–testing paradigm, to investigate whether or not healthy subjects show less activation to the second voice stimulus. Seventeen healthy adults (mean age 27.9 ± 4.8 years, 9 males and 8 females) participated in the experiment. The auditory stimuli were presented monaurally as a series of 120 paired voices, with 500-ms interstimulus intervals and 6-s interpaired stimulus intervals. The P50m and the N100m responses were investigated, and dipole source localization was performed. Root mean squares of both P50m and N100m were significantly suppressed to the second stimulus bilaterally, and the suppression was more significant in N100m. The N100m was located significantly more laterally than the P50m for both hemispheres. These results therefore demonstrate the presence of sensory gating for auditory inputs of the human voice in the primary auditory cortex and the auditory association area.

P50 auditory sensory gating in first onset schizophrenics and normal healthy adults

The aim of this research was to investigate the variations of P50 auditory sensory gating (P50) in normal healthy adults and the first onset schizophrenics. By using the American Nicolet Bravo electromyography/evoked potential (EMG/EP) system, P50 was measured with conditioning-testing paradigm (paired-click stimuli S1 and S2 were used) in 58 first onset schizophrenics and 108 healthy adults, and the Positive and Negative Syndrome Scale (PANSS) was applied. The following three conclusions have been reached. (1) In normal control (NC) group, measured from central, anterior and posterior zone (Cz, Fz and Pz respectively), there were no statistical differences (P > 0.05) between S1 and S2 evoked P50 peak latencies (S1-P50 and S2-P50); the amplitudes of S2-P50 [(2.2 ± 1.4), (2.3 ± 1.5) and (2.1 ± 1.4) μV respectively] reduced significantly as compared with S1-P50 [(5.6 ± 3.3), (5.6 ± 3.9) and (4.9 ± 2.8) μV respectively] (P < 0.01); the S2/S1 ration, S1-S2 difference, and 100 (1-S2/S1) had no statistical differences (P > 0.05). (2) Compared with NC, the schizophrenic group significantly showed lower S1-P50 amplitudes (P < 0.01, except at Pz in which Z = 2.030, P = 0.042), higher S2-P50 amplitudes, higher S2/S1 ratio, lower S1-S2 difference, and more decreased 100 (1-S2/S1) (P < 0.01) at Cz, Fz and Pz. (3) No significant correlations were found among S2/S1 ratio, S1-S2, 100 (1-S2/S1) of sensory gating and PANSS (P > 0.05) in schizophrenic group. The first onset schizophrenics had sensory gating deficits, which could be quantified by P50.

P50 inhibitory gating deficit is correlated with the negative symptomatology of schizophrenia

Abnormal sensory gating in schizophrenia has frequently been reported. The strength of central inhibitory pathways was measured using the P50 component of the auditory evoked potential in a conditioning–testing paradigm. The relationships between a relative decrease in P50 amplitude to repeated auditory stimuli and clinical symptoms remain controversial. Using the Positive and Negative Syndrome Scale, we studied the P50 auditory conditioning–testing paradigm in 81 schizophrenic subjects, categorized into subgroups with and without prominent negative symptoms, in comparison with 88 control subjects. We found increased ratios of testing stimuli to conditioning stimuli in both schizophrenic subgroups relative to findings in the control group. In addition, we found significantly increased mean latencies of the P50 responses to conditioning (C) and testing (T) stimuli and significantly increased T/C ratios in the subgroup with negative symptoms compared with the subgroup with non-negative symptoms.

Neural correlates of sensory gating in the rat: decreased Fos induction in the lateral septum

In the P 50 gating or conditioning-testing paradigm in the rat, two identical click stimuli are presented with an inter-click interval of 500 ms. The reaction towards the second click, as measured with evoked potentials, is reduced in respect to that towards the first click; this phenomenon is called sensory gating. In the present experiments, the inter-click interval was varied systematically and auditory evoked potentials were measured. Sensory gating was found to occur only at intervals between 500 and 1000 ms, but not at longer intervals. Fos immunohistochemistry was then performed using two groups of rats exposed to double clicks: the inter-click interval was 500 ms in the experimental group and 2500 ms in the control group. Fos induction was analyzed in selected brain structures. In the auditory pathways, Fos-immunoreactive neurons were found in both groups of rats in the inferior colliculus and medial geniculate body. Fos-immunoreactive cells were also examined in the septum and hippocampus. In the ventral part of the lateral septal nucleus, the labeled neurons were significantly fewer in the experimental animals compared to the control group. Smaller and non-significant quantitative differences of Fos-positive neurons were documented in the medial septum and hippocampal CA1 region. These data point out a selective decrease in the lateral septum of Fos induced by auditory sensory gating, and suggest an involvement of this structure, and possibly of other parts of the septo-hippocampal system, in sensory gating mechanisms. The results might be relevant for theories on sensory gating deficits in schizophrenia.

The P50 auditory event–evoked potential in adult attention-deficit disorder: comparison with schizophrenia

Background: Attention-deficit/hyperactivity disorder (ADHD) and schizophrenia are both conceptualized as disorders of attention. Failure to inhibit the P50 auditory event–evoked response, extensively studied in schizophrenia, could also occur in ADHD patients, if these two illnesses have common underlying neurobiological substrates. Methods: This study examined the inhibition of the P50 auditory event–evoked potential in 16 unmedicated adults with ADHD, 16 schizophrenic outpatients, and 16 normal control subjects. Auditory stimuli were presented in a paired stimulus, conditioning-testing paradigm. Results: The amplitude of initial or conditioning P50 response did not differ between the three groups; however, significant effects of psychiatric diagnosis on the amplitude of the test response and the ratio of the test to the conditioning response amplitudes were observed. Schizophrenic patients’ P50 ratios and test amplitudes were higher than both the ADHD and normal groups. Conclusions: Adults with ADHD do not have the inhibitory deficit seen in patients with schizophrenia, suggesting that the mechanism of attentional disturbance in the two illnesses may be fundamentally different.

The effect of firing on the excitability of a model motoneurone and its implications for cortical stimulation.

1. To help clarify the use of measurements of 'excitability', a simple model motoneurone receiving noisy tonic background excitation was tested with brief stimuli. Its response was determined from its PSTH (post-stimulus time histogram). The tonic background was varied from well below to well above the threshold for tonic firing. The conclusions should apply to many other neurones. 2. The response of the model to a stimulus depended upon a number of factors, including stimulus strength, synaptic membrane noise and especially whether or not the background drive elicited tonic firing. With the onset of firing, the shape of the stimulus-response curve changed drastically and the model then responded to the smallest stimulus without a threshold. When the drive was subthreshold, increasing the background excitation always increased the response to a given stimulus. However, what happened when the tonic drive exceeded the threshold for tonic firing depended upon the stimulus strength. With weak stimuli, the response increased with the drive to reach a plateau level where it was independent of the background firing rate; this occurred for stimuli comparable in size to the synaptic noise. With stronger stimuli, the response rose to a maximum for very low firing rates, but then decreased by up to 50 % to a plateau for high firing rates. Increasing the membrane noise reduced or abolished the maximum. 3. The model was also used to simulate a monosynaptic conditioning-testing paradigm. The effect of a given conditioning stimulus was then found to change with the onset of firing, including when the strength of the testing stimulus was adjusted to make the size of the test response the same in the presence and absence of firing. 4. The behaviour of real motoneurones can be expected to be at least as complex with the transition from silence to firing, so H reflex and other tests of 'excitability' must then be treated with caution. In particular, as has been observed experimentally, the response of a unit may decrease with increasing background excitation, as well as with inhibition. 5. Transferring the findings to corticospinal neurones makes it unlikely that the magnitude of the descending volley elicited by a given cortical stimulus ('excitability') will always increase with the initial level of cortical activity. In addition, the appreciable threshold for transcranial magnetic stimulation during voluntary contraction suggests that it first excites axons rather than the neural pacemakers.

Differential effects of ketamine on gating of auditory evoked potentials and prepulse inhibition in rats.

Schizophrenic patients suffer from deficits in information processing. Patients show both a decrease in P50 gating [assessed in the conditioning-testing (C-T) paradigm] and prepulse inhibition (PPI), two paradigms that assess gating. These two paradigms might have a related underlying neural substrate. Gating, as measured in both the C-T paradigm (the gating of a component of the auditory evoked potential (AEP)], and PPI can easily be measured in animals as well as in humans. This offers the opportunity to model these information processing paradigms in animals in order to investigate the effects of neurotransmitter manipulations in the brain. In order to validate the animal model for disturbances in AEP gating, d-amphetamine (0.5 and 1 mg/kg, i.p.) was administered. Gating of an AEP component was changed due to injection of d-amphetamine (1 mg/kg) in the same way as seen in schizophrenic patients: both the amplitude to the conditioning click and the gating were significantly reduced. Next, the effect of the N-methyl-D-aspartate (NMDA) antagonist ketamine (2.5 and 10 mg/kg, i.p.) was investigated to assess its effects in the two gating paradigms. It was found that ketamine (10 mg/kg) did not affect gating as measured with components of the AEP. However, ketamine (10 mg/kg) disrupted PPI of the startle response to the extent that prepulse facilitation occurred. Firstly, it is concluded that AEP gating was disrupted by d-amphetamine and not by ketamine. Secondly, PPI and the C-T paradigm reflect distinct inhibitory sensory processes, since both paradigms are differentially influenced by ketamine.

A comparison of the repetitive click and conditioning-testing P50 paradigms

The auditory P50 ERP component has previously been studied either in the repetitive click or the conditioning-testing (C-T) paradigm. For 20 subjects, we compared 4 repetitive click and 4 C-T protocols in a single experimental session with identical recording techniques and with interclick intervals comparable to the C-T intervals. In the C-T protocols, a long interval between click pairs ensured full recovery of P50 to the C click. The analysis of P50 topographies provided strong evidence that the same component was measured in the two paradigms. For both paradigms, P50 amplitude was progressively suppressed as the interclick or C-T interval decreased ( P<0.0001), with parallel interval vs. P50 amplitude regression lines for the two paradigms. There was a strong trend ( P=0.08) for the repetitive click amplitudes to be smaller than T amplitudes for comparable repetitive click and C-T intervals. Equivalently, this strong trend suggests that repetitive click intervals must be longer (by about 300 ms) than the C-T interval to generate equivalent amplitude P50 responses. We conclude that the same component is measured in both paradigms, that P50 amplitude decreases with decreasing interstimulus intervals in both paradigms, and that in normals, for comparable inter-click and C-T intervals, there is greater P50 suppression in the repetitive click paradigm. Finally, we note that the comparison of paradigms within normals does not necessarily apply to clinical samples.

Replication of a P50 auditory gating deficit in Australian patients with schizophrenia

Schizophrenic patients reportedly have a deficit in the control of sensitivity to auditory stimuli as shown by the P50 auditory evoked potential wave in a conditioning-testing paradigm that measures suppression of response to a repeated stimulus. Although this finding has been replicated by several US laboratories, one European group has not found differences between schizophrenic patients and normal control subjects. In the present study, investigators in the Schizophrenia Research Center at the Prince of Wales Hospital in Sydney, Australia, selected 22 normal control subjects, 11 acutely ill schizophrenic inpatients, and 11 clinically stable schizophrenic outpatients. Both schizophrenic groups were treated with similar doses of classical neuroleptic medications. Evoked potentials were recorded by an investigator from the US laboratory that initially reported the difference; five averages, each the response to 32 stimulus pairs, were recorded from each subject. The normal control subjects demonstrated significantly more suppression of the P50 response to the repeated stimuli than the schizophrenic groups, as previously reported. There were no significant changes in the suppression measure over the five trials. The suppression of the P50 wave by schizophrenic outpatients was somewhat greater than that by schizophrenic inpatients, but both schizophrenic groups had decreased suppression, compared with the normal subjects. The mean P50 suppression for five averages was successfully used in a logistic regression to classify subjects as normal or schizophrenic. This method was more accurate than attempts to classify subjects with only one average. The mean amplitude of the initial conditioning response did not differ between groups. Schizophrenic patients had slightly shorter mean latencies. There was no direct relationship of P50 suppression to measures of clinical psychopathology.

Gender differences in gating of the auditory evoked potential in normal subjects

Central nervous system (CNS) inhibitory mechanisms hypothesized to "gate" repetitive sensory inputs have been implicated in the pathology of schizophrenia. The present study investigated gender differences in inhibitory gating of evoked brain responses to repeated stimuli in normal subjects (30 women and 30 men) using an auditory conditioning-testing paradigm. Pairs of click stimuli (S1 and S2) were presented with a 0.5 s intrapair and a 10 s interpair interval. The amplitudes and latencies of the P50, N100, P180 components of the auditory evoked response to the conditioning (S1) and test response (S2) were measured, and the gating ratios were computed (T/C ratio = S2/S1 * 100). The amplitudes to S1 were not significantly different between men and women at P50, N100, or P180. However, women had significantly higher amplitudes to S2 at P50 (p = 0.03) and N100 (p = 0.04). The T/C ratios for women were higher (i.e., less suppression of response to S2) for P50 (p = 0.08) and N100 (p = 0.04) compared to men. The results suggested that differences in auditory gating between men and women were not due to biological differences in the P50 and N100 generators but possibly to differential influence of inhibitory mechanisms acting on the generator substrates of these evoked responses.