Gating Of Auditory Evoked Potentials Research Articles

Impairment in Mismatch Negativity but not Repetition Suppression in Schizophrenia.

Schizophrenia is characterized by impaired auditory-evoked potentials (AEPs), mismatch negativity (MMN), and sensory gating of AEPs to repeated stimuli (repetition suppression, RS). In the predictive modeling framework, MMN and RS reflect encoding of prediction error and model sharpening, respectively. We compared P50, N100, P200 RS, and pitch and duration MMN in 26 participants diagnosed with schizophrenia (SZ) and 26 matched healthy controls (HC), and assessed relationships between MMN, RS, and SZ diagnosis. RS was measured by comparing responses to individual tones presented as 5-tone groups (1kHz, 75 dB, 50ms, 5ms rise/fall times, 330ms SOA), separated by a 750ms inter-trial interval. For MMN, the same tones were presented, with occasional pitch (1.2kHz, 10%) or duration deviants (100ms, 10%) interspersed. Pitch and duration MMN were reduced in SZ (p < 0.01). There were no group differences in P50 RS, N100 RS, or P200 RS (p's > 0.1). Importantly, although pitch and duration MMN both correlated with RS of AEPs within the MMN time range (p's < 0.01), SZ diagnosis predicted MMN over and above RS (p < 0.05) and shared little variance with RS in prediction of MMN amplitude (tolerance > 0.93). We suggest that reduced MMN in SZ is related to deficits in encoding prediction error but not repetition suppression.

Early Auditory Sensory Processing Deficits in Mouse Mutants with Reduced NMDA Receptor Function

Cognitive deficits in schizophrenia include impairments at automatic, preattentive stages of sensory information processing. These deficits are evident in the prepulse inhibition- (PPI) and habituation of the auditory startle response paradigm, the paired tone paradigm in the EEG, and the peak recovery function of auditory evoked potentials (AEP). Administration of NMDA receptor antagonists reliably disrupts PPI and habituation of the startle, but not gating of AEPs in rodents. In the peak recovery paradigm, patients with schizophrenia and primates treated with NMDA receptor antagonists show reduced maximal response at long interstimulus intervals (ISI), but normal responses at short ISIs. Thus reduced NMDA receptor signalling may underlie alterations in these paradigms observed in schizophrenia. We tested the paradigms mentioned in mouse mutants with reduced expression of the NR1 subunit of the NMDA receptor (N = 15) and their wild-type littermates (N = 16). The NR1 mutant mice showed impaired habituation and PPI of the auditory startle response, as well as impaired gating in the paired tone paradigm. Deficits between the two gating measures did not correlate, corroborating previous evidence that these paradigms measure distinct processes. In the peak recovery paradigm, the NR1 mutants showed increased responses of the AEPs P1 and N1 at short ISIs but no difference between groups were observed at long ISIs. In conclusion, the NR1 hypomorphic mice modelled sensory and sensorimotor gating and startle habituation deficits observed in schizophrenia, but failed to model alterations in the peak recovery function.

Nicotine and clozapine selectively reverse a PCP-induced deficit of PPI in BALB/cByJ but not NMRI mice: Comparison with risperidone

Schizophrenic patients have deficits in prepulse inhibition (PPI) that may be alleviated by smoking/nicotine. The effect of nicotinic agents on PPI in rodents is equivocal and few studies in mice have been reported. Thus, we assessed nicotine's (0.03–1 mg/kg) effect on PPI in five mouse strains with no effects. We next determined if nicotine would reverse a phencyclidine (PCP)-induced deficit of PPI in BALB/cByJ and NMRI mice. BALB/cByJ mice have a low density of [ 125I]α-bungaratoxin binding in the hippocampus and poor inhibitory gating of auditory evoked potentials (AEPs), a model related to PPI. At 1 mg/kg, nicotine selectively reversed the PCP-induced deficit of PPI in BALB/cByJ mice. The pharmacokinetic profile of nicotine ( T 1/2, C max, T max and AUC) was identical in both strains, obviating this as a factor for the strain-dependent effect observed. Moreover, 1 mg/kg nicotine inhibited in vivo [ 3H]epibatidine binding with the same time-course in both strains, indicating no difference in brain “kinetics”. Since high doses of nicotine were effective in BALB/cByJ mice a role for low-affinity nicotinic receptors, e.g. α 7 receptors, is plausible. Clozapine, but not risperidone, also only reversed the PCP deficit of PPI in BALB/cByJ. Clozapine and nicotine also enhance inhibitory gating of AEPs in DBA/2 mice, and clozapine's effect is antagonized by an α 7 antagonist. Our data and previous evidence possibly suggest a role for low-affinity nicotinic receptors in the effects of clozapine and nicotine. Furthermore, BALB/cByJ mice may represent a model to test the effects of nicotinic agents acting at low-affinity nicotinic receptors.

Scalp recordings of mid-latency AEP and auditory gating in the Göttingen minipig: a new animal model in information processing research

Early central information processing, measured in humans by the gating of the middle latency auditory evoked potential (AEP) P50 and the effect of attention on AEP N100, is affected in schizophrenia. Exploring the possibility of using miniature pigs in longitudinal studies of chronic neuropsychiatric disorders, we present a method for recording seven channel surface middle latency AEP in the awake animal. The AEP and the AEP gating measured in a paired stimulus paradigm similar to the P50 gating paradigm used in humans, were recorded in six adult male minipigs in two sessions. The AEP had a stable N40/P60/N120/P200 configuration and in the gating paradigm the difference between stimulus one (S1) and two (S2) P60 and N120 amplitudes were significant. Mean AEP P60 gating ratio (S2/S1) at the posterior central electrode was 0.66 (std 0.29) range 0.21–1.08 and corresponding N120 was 0.60 (std 0.19) range 0.28–0.76. The method presented is feasible for scalp recordings of middle latency evoked potentials in the awake animal, but further studies of interval sensitivity and the effect of arousal manipulation are needed to assess the equivalence of the pig components to those of the human at similar latencies.

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.

Sensory gating in rats: lack of correlation between auditory evoked potential gating and prepulse inhibition.

This study was designed to evaluate the possible similarities between two paradigms designed to measure sensory gating: (1) an auditory evoked potential (AEP), called the P50 gating paradigm; and (2) an acoustic startle (ASR), called the prepulse inhibition paradigm. These paradigms show a number of methodological, pharmacological, and neurobiological similarities, and they are both disturbed in patients with schizophrenia. In the first of three experiments, the AEP gating and the ASR gating were measured in rats. Although both AEP and ASR gating could readily be obtained, there appeared to be no correlation between the performance in these two paradigms. This lack of correlation was confirmed using a factor analytical approach, where the AEP gating and the ASR gating parameters were found to load on different factors. In the second experiment, the interstimulus interval in the ASR paradigm was increased to 500 ms (identical to the interstimulus interval of the AEP gating paradigm). This increase reduced the degree of ASR gating, although some gating could still be obtained. Again no correlation was found between AEP and ASR gating, and this was again confirmed by the factorial analysis. In the final experiment, the effects of the dopamine D2/3 agonist 7-OHDPAT were evaluated in both paradigms. This selective agonist dose dependently reduced ASR gating but had no effect on AEP gating. Together, these data strongly suggest that AEP and ASR gating measure two different aspects of information processing and indicate that both paradigms may be important for investigating the neurobiological disturbances observed in patients with psychoses.