Comparison of four components of sensory gating in schizophrenia and normal subjects: a preliminary report

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 ¼ 15) and their wild-type littermates (N ¼ 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.

Section: Auditory Gatingmentioning

confidence: 84%

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

Bickel

Lipp

Umbricht

2007

“…Although the P50 component is often used to examine sensory gating in schizophrenia, the N100 is also a sensitive measure of sensory gating (Boutros et al, 1999). The interstimulus interval paradigm used to evaluate the mouse ERP components in this study has been described as a stable measure of sensory gating in schizophrenia (Erwin et al, 1994;Javitt et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, some patients with schizophrenia show an impaired gating of auditory evoked potentials (Boutros et al, 1999;Erwin et al, 1994;Stevens et al, 1997). Sensory gating refers to the ability of the brain to modulate its sensitivity to the incoming sensory stimuli (Braff and Geyer, 1990).…”

Section: Introductionmentioning

confidence: 99%

“…Two tasks that measure the sensory gating of event-related potentials (ERPs) are the paired click paradigm, as a transient gating measure, and the interstimulus interval paradigm (ISI), as a steady-state gating measure (Erwin et al, 1994). The paired click paradigm contains two tones presented 500 ms apart with a 9-s interval between pairs, while the ISI task typically utilizes trains of stimuli at short intervals ranging from 0.25 to 1 s and longer intervals ranging from 2 to 10 s. During the ISI task in human studies, the amplitude of the N100 decreases with decreasing interstimulus intervals in healthy individuals (Boutros et al, 1999;Javitt et al, 2000). In contrast to the N100, the amplitude of the human P50 does not increase with increasing interstimulus intervals ranging from 1 to 16 s (Javitt et al, 2000;McFarland et al, 1975;Onitsuka et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Chronic Olanzapine and Haloperidol Differ on the Mouse N1 Auditory Evoked Potential

Maxwell

Liang

Weightman

et al. 2004

Auditory evoked potentials have been used in a variety of animal models to assess information-processing impairments in schizophrenia. Previous mouse models have primarily employed a paired click paradigm to assess the transient measures of auditory gating. The current study uses stimulus trains at varied interstimulus intervals (ISI) between 0.25 and 8 s in mice to assess the effects of chronic olanzapine and haloperidol on auditory processing. Data indicate that olanzapine increases the amplitude of the N40, P80, and P20/N40 components of the auditory evoked potential, whereas haloperidol had no such effect. The ISI paradigm also allowed for an evaluation of several components of the mouse evoked potential to assess those that display response properties similar to the human P50 and N100. Data suggest that the mouse N40 displays an ISI response relationship that shares characteristics with the human N100, whereas the P20 appears more consistent with the human P50 across the ISI range evaluated in this task. This study suggests that olanzapine may help improve N100 impairments seen in schizophrenia, while haloperidol does not.

“…In humans, it is mainly the P50 event-related potential (ERP, a positive deflection seen in the EEG~50 ms after a response-eliciting stimulus) also sometimes referred to as the P1 amplitude that is scored to express sensory gating (Chang et al, 2011). However, in addition the succeeding N100 (or N1, a negative ERP at 100 ms) and P200 (or P2) have been used to assess sensory gating (Boutros et al, 1999), although there is different underlying neural activity involved (Boutros et al, 2004;Brockhaus-Dumke et al, 2008;Oranje et al, 2006). Similar to humans, other animal species such as primates, cats, rabbits, rats, and mice display sensory gating.…”

Section: Introductionmentioning

confidence: 99%

Comparing Pharmacological Modulation of Sensory Gating in Healthy Humans and Rats: The Effects of Reboxetine and Haloperidol

Witten

Bastlund

Glenthøj

et al. 2015

Sensory gating is the brain's ability to filter out irrelevant information before it reaches high levels of conscious processing. In the current study we aimed to investigate the involvement of the noradrenergic and dopaminergic neurotransmitter systems in sensory gating. Furthermore, we investigated cross-species reliability by comparing effects in both healthy humans and rats, while keeping all experimental conditions as similar as possible between the species. The design of the human experiment (n = 21) was a double-blind, placebocontrolled, cross-over study where sensory gating was assessed following a dose of either reboxetine (8 mg), haloperidol (2 mg), their combination or placebo at four separate visits. Similarly in the animal experiment sensory gating was assessed in rats, (n = 22) following a dose of reboxetine (2 mg/kg), haloperidol (0.08 mg/kg), their combination or placebo. The sensory gating paradigms in both experiments were identical. In humans, we found significantly reduced P50 suppression following separate administration of reboxetine or haloperidol, while their combined administration did not reach statistical significance compared with placebo. In the rats, we found a similar significant reduction of sensory gating (N40) following treatment with haloperidol and the combination of haloperidol and reboxetine, but not with separate reboxetine treatment, compared with placebo. Our study indicates that even when experimental conditions are kept as similar as possible, direct human to rat cross-species translation of pharmacological effects on sensory gating is challenging, which calls for more focussed research in this important translational area.