Gating of auditory response in schizophrenics and normal controls: Effects of recording site and stimulation interval on the P50 wave

doi:10.1016/0920-9964(91)90007-E

Schizophrenia Research

Volume 4, Issue 1, January–February 1991, Pages 31-40

https://doi.org/10.1016/0920-9964(91)90007-E Get rights and content

Abstract

Auditory evoked potentials were recorded using a paired stimulus, conditioning-testing paradigm from 14 schizophrenic patients and 13 normal subjects with no family history of psychotic disorder. Previous studies of the vertex P50 wave using this paradigm have demonstrated a possible sensory gating deficit in schizophrenics, as shown by their failure to diminish the response to a test stimulus presented 500 ms after a conditioning stimulus. Recordings were made at Cz, Fz, C3, T3, C4, and T4, to compare effects at different recording sites with this paradigm. Schizophrenics had significantly poorer sensory gating than normals, with the most significant difference between the groups at Cz. In addition to the 500 ms interval, subjects were also recorded at a conditioning-testing interval of 100 ms. Most schizophrenics showed normal sensory gating at the 100 ms interval, despite their abnormalities at 500 ms. The results indicate that Cz is an optimal recording site for this paradigm, and that gating abnormalities in schizophrenic subjects are limited to specific interstimulus intervals.

References (46)

L.E. Adler et al.
Neurophysiological studies of sensory gating in schizophrenia: Comparisons of auditory and visual responses
Biol. Psychiatry
(1985)
N. Baker et al.
Neurophysiological assessment of sensory gating in psychiatric inpatients; Comparison between schizophrenia and other diagnoses
Biol. Psychiatry
(1987)
B.M. Chen et al.
Midlatency auditory evoked responses: Differential effects of sleep in the cat
Electroencephalogr. Clin. Neurophysiol.
(1986)
J.H. Gruzelier
The cardiac responses of schizophrenics to orienting, signal, and non-signal tones
Biol. Psychiatry
(1975)
C.L. Hinman et al.
Depth evoked potential and single unit correlates of vertex midlatency auditory evoked responses
Brain Res.
(1983)
R.T. Knight et al.
The effects of lesions of superior temporal gyrus and inferior parietal lobe on temporal and vertex components of the human AEP
Electroencephalogr. Clin. Neurophysiol.
(1988)
D.F. Lindsley et al.
Availability of peripheral input to the midbrain reticular formation
Exp. Neurol.
(1961)
H.T. Nagamoto et al.
Sensory gating in schizophrenics and normal controls: Effects of changing stimulation interval
Biol. Psychiatry
(1989)
M. Reite et al.
Source origin of a 50-msec latency auditory evoked field component in young schizophrenic men
Biol. Psychiatry
(1988)
M. Schwartz et al.
Reticular modification of somatosensory cortical recovery function
Electroencephalogr. Clin. Neurophysiol.
(1963)

C.C. Wood et al.

Scalp distribution of human auditory evoked potentials. II. Evidence for overlapping sources and involvement of auditory cortex

Electroencephalogr. Clin. Neurophysiol.

(1982)

D.L. Woods et al.

Generators of middle- and long-latency auditory evoked potentials: implications from studies of patients with bitemporal lesions

Electroencephalogr. Clin. Neurophysiol.

(1987)

L.E. Adler et al.

Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating and schizophrenia

Biol. Psychiatry

(1982)

N.J. Baker et al.

Family diagnoses missed on a clinical inpatient service

Am. J. Psychiatry

(1987)

P.C. Bickford-Wimer et al.

Auditory sensory gating in hippocampal neurons: A model system in the rat

Biol. Psychiatry

(1989)

E. Bleuler

Dementia Praecox or the Group of Schizophrenias

(1950)

D. Braff et al.

Regional erp/attention deficits in schizophrenia

Abstracts from Annual Meeting of the Society of Biological Psychiatry

(1987)

D. Braff et al.

Effect of antipsychotic medication: Speed of information processing in schizophrenic patients

Am. J. Psychiatry

(1982)

D. Braff et al.

Prestimulus effects on human startle reflex in normals and schizophrenics

Psychophysiology

(1982)

E. Callaway

Brain Electrical Potentials and Individual Psychological Differences

(1975)

G. D'Elia

Unilateral Electroconvulsive Therapy

Acta Psychiatr. Scand.

(1970)

J.C. Eccles

The Inhibitory Pathways of the Central Nervous System

(1969)

R.D. Franks et al.

Neurophysiological studies of sensory gating in mania: Comparison with schizophrenia

Biol. Psychiatry

(1983)

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Paired-stimuli (S1-S2) procedures have long been used to assess auditory processing in psychosis. Such studies have shown aberrant evoked responses (ERPs) following long (S1 response) and/or short (S2 response) inter-stimulus intervals. The historical tendency from paired stimuli outcomes in the schizophrenia (SZ) literature is for (i) response to the first stimulus (S1) to be smaller among SZ, and (ii) response to the second stimulus (S2) to be larger among SZ in relation to the size of their S1. An interpretation of these two findings is that SZ have poor auditory response suppression to redundant stimuli (“poor gating”). The present study sought to determine if the reported S1 and S2 effects in SZ (smaller S1 and larger S2 in relation to S1 magnitude) require the paired-stimuli presentation format. Participants (18 schizophrenia and 17 healthy persons) were administered the equivalent of S1 (after a 4.5-sec ISI – “long ISI”) and S2 (after a 500-ms ISI – “short ISI”) stimuli under four conditions (traditional paired long and short, randomly interleaved long and short, block of long, block of short). Neural activity differences were consistent between-groups independent of condition: (i) schizophrenia cases had greater activity in the pre-stimulus to very early post-stimulus period, (ii) healthy persons had greater M100 activity to long ISI stimuli, and (iii) healthy persons had greater activity after the M50/M100 evoked fields (recovery phase) following short ISI stimuli. Simple early auditory processing in psychosis may be largely independent of stimulus presentation condition, an outcome that may help re-frame future translational studies. Traditional paired-stimuli auditory neural response effects may not require the paired-stimuli format.
Methodological considerations for a better somatosensory gating paradigm: The impact of the inter-stimulus interval
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Sensory gating (SG) is a neurophysiological phenomenon whereby the response to the second stimulus in a repetitive pair is attenuated. This filtering of irrelevant or redundant information is thought to preserve neural resources for more behaviorally-relevant stimuli and thereby reflect the functional inhibition of sensory input. Developing a SG paradigm in which optimal suppression of sensory input is achieved requires investigators to consider numerous parameters such as stimulus intensity, time between stimulus pairs, and the inter-stimulus interval (ISI) within each pair. While these factors have been well defined for the interrogation of auditory gating, the precise parameters for eliciting optimal gating in the somatosensory domain are far less understood. To address this, we investigated the impact of varying the ISI within each identical pair of stimuli on gating using magnetoencephalography (MEG). Specifically, 25 healthy young adults underwent paired-pulse electrical stimulation of the median nerve with increasing ISIs between 100 and 1000 ms (in 100 ms increments). Importantly, for correspondence with previous studies of somatosensory gating, both time-domain and oscillatory neural responses to somatosensory stimulation were evaluated. Our results indicated that gating of somatosensory input was optimal (i.e., best suppression) for trials with an ISI of 200–220 ms, as evidenced by the smallest gating ratios and through statistical modeling estimations of optimal suppression. Importantly, this was true irrespective of whether oscillatory or evoked neural activity was used to calculate SG. Interestingly, oscillatory metrics of gating calculated using peak gamma (30-75 Hz) power and frequency revealed more robust gating (i.e., smaller ratios) than those calculated using time-domain neural responses, suggesting that high frequency oscillations may provide a more sensitive measure of SG. These findings have important implications for the development of optimal protocols and analysis pipelines to interrogate SG and inhibitory processing with a higher degree of sensitivity and accuracy.
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Citation Excerpt :
In addition, studies with overlapping samples were excluded from further analysis, furthermore only first estimation was included from the studies that had repeated estimations of P50 sensory gating in a group. 115 articles (Adler et al., 2005; Adler et al., 1990a; Adler et al., 2004; Adler et al., 1982; Adler et al., 1985; Adler et al., 1990b; Arango et al., 2003; Arnfred et al., 2003; Arnfred et al., 2004; Bak et al., 2014; Baker et al., 1987; Becker et al., 2004; Becker et al., 2011; Boutros et al., 1999; Boutros et al., 2009; Boutros et al., 2004; Boutros et al., 1991; Braff et al., 2007; Brenner et al., 2009; Brockhaus-Dumke et al., 2008a; Brockhaus-Dumke et al., 2008b; Brunstein et al., 2005; Buchanan et al., 2003; Cabranes et al., 2013; Chen et al., 2011; Clementz and Blumenfeld, 2001; Clementz et al., 1997a; Clementz et al., 1997b, 1998a, b; Cullum et al., 1993; Dalecki et al., 2016; de Wilde et al., 2007a; Demily et al., 2016; Devrim-Ucok et al., 2008; Domjan et al., 2012; During et al., 2014; El-Kaim et al., 2015; Franks et al., 1983; Freedman et al., 1987; Fresan et al., 2007; Ghisolfi et al., 2006; Ghisolfi et al., 2004; Ghisolfi et al., 2002; Gjini et al., 2010; Gjini et al., 2011; Griffith and Freedman, 1995; Griffith et al., 1998; Griffith et al., 1993; Hall et al., 2015; Hall et al., 2014; Hong et al., 2008a; Hong et al., 2004; Hong et al., 2007; Hong et al., 2009; Hsieh et al., 2004; Jin et al., 1998; Johannesen et al., 2005; Johannesen et al., 2013; Judd et al., 1992; Kathmann and Engel, 1990; Keri et al., 2010; Kim et al., 2018; Kisley and Cornwell, 2006; Koike et al., 2005; Light et al., 2000; Louchart-de la Chapelle et al., 2005a; Louchart-de la Chapelle et al., 2005b; Lu et al., 2007; Martin et al., 2007a; Mazhari et al., 2011; Micoulaud-Franchi et al., 2015a; Micoulaud-Franchi et al., 2012; Micoulaud-Franchi et al., 2015b; Micoulaud-Franchi et al., 2014; Micoulaud-Franchi et al., 2015c; Moran et al., 2012; Myles-Worsley, 2002; Nagamoto et al., 1996; Nagamoto et al., 1999; Nagamoto et al., 1989; Nagamoto et al., 1991; Neuhaus et al., 2014; Olincy et al., 2010; Olincy and Martin, 2005; Olincy et al., 2000; Oranje and Glenthoj, 2014; Patterson et al., 2009; Price et al., 2006; Rentzsch et al., 2007; Ringel et al., 2004; Sanchez-Morla et al., 2008; Sanchez-Morla et al., 2013; Sanchez-Morla et al., 2009; Santos et al., 2010; Shan et al., 2013; Siegel et al., 1984; Smith et al., 2010; Smith et al., 2013; Smucny et al., 2013; Song et al., 2014; Storozheva et al., 2016; Thoma et al., 2003; Thoma et al., 2008; Toyomaki et al., 2015; Turetsky et al., 2009; Vinogradov et al., 1996; Waldo et al., 1992; Waldo et al., 1988; Waldo et al., 1994; Waldo et al., 2010; Waters et al., 2009; Williams et al., 2011; Wonodi et al., 2014; Yee et al., 1998; Yee et al., 2010; Zhang et al., 2012) were included in schizophrenia, 16 studies (Adler et al., 1990a; Ancin et al., 2011; Cabranes et al., 2013; Carroll et al., 2008; Domjan et al., 2012; Franks et al., 1983; Hall et al., 2015; Hall et al., 2014; Hall et al., 2008; Johannesen et al., 2013; Lijffijt et al., 2009; Martin et al., 2007a; Olincy and Martin, 2005; Patterson et al., 2009; Sanchez-Morla et al., 2008; Schulze et al., 2007) were included in bipolar disorder, 10 study groups (in 9 studies) in first-degree relatives (Clementz et al., 1998b; de Wilde et al., 2007a; Hall et al., 2008; Hong et al., 2008b; Louchart-de la Chapelle et al., 2005b; Myles-Worsley, 2002; Olincy et al., 2010; Schulze et al., 2007; Siegel et al., 1984) and 110 studies included healthy controls (Adler et al., 1990a; Adler et al., 2004; Adler et al., 1982; Adler et al., 1985; Adler et al., 1990b; Arnfred et al., 2003; Arnfred et al., 2004; Bak et al., 2014; Baker et al., 1987; Becker et al., 2004; Becker et al., 2011; Boutros et al., 1999; Boutros et al., 2009; Boutros et al., 2004; Braff et al., 2007; Brenner et al., 2009; Brockhaus-Dumke et al., 2008a; Brockhaus-Dumke et al., 2008b; Cabranes et al., 2013; Carroll et al., 2008; Chen et al., 2011; Clementz and Blumenfeld, 2001; Clementz et al., 1997a; Clementz et al., 1997b, 1998a, b; Cullum et al., 1993; Dalecki et al., 2016; de Wilde et al., 2007a; Demily et al., 2016; Devrim-Ucok et al., 2008; Domjan et al., 2012; During et al., 2014; El-Kaim et al., 2015; Franks et al., 1983; Freedman et al., 1987; Fresan et al., 2007; Ghisolfi et al., 2006; Ghisolfi et al., 2004; Ghisolfi et al., 2002; Gjini et al., 2010; Gjini et al., 2011; Griffith and Freedman, 1995; Griffith et al., 1993; Hall et al., 2015; Hall et al., 2014; Hall et al., 2008; Hong et al., 2004; Hong et al., 2008b; Hong et al., 2007; Hong et al., 2009; Hsieh et al., 2004; Hsieh et al., 2012; Jin et al., 1998; Johannesen et al., 2005; Johannesen et al., 2013; Judd et al., 1992; Kathmann and Engel, 1990; Keri et al., 2010; Kisley and Cornwell, 2006; Koike et al., 2005; Lijffijt et al., 2009; Louchart-de la Chapelle et al., 2005a; Louchart-de la Chapelle et al., 2005b; Lu et al., 2007; Martin et al., 2007a; Mazhari et al., 2011; Micoulaud-Franchi et al., 2015a; Micoulaud-Franchi et al., 2012; Micoulaud-Franchi et al., 2014; Moran et al., 2012; Myles-Worsley, 2002; Nagamoto et al., 1989; Nagamoto et al., 1991; Neuhaus et al., 2014; Olincy et al., 2010; Olincy and Martin, 2005; Olincy et al., 2000; Oranje and Glenthoj, 2014; Price et al., 2006; Rentzsch et al., 2007; Ringel et al., 2004; Sanchez-Morla et al., 2008; Sanchez-Morla et al., 2013; Sanchez-Morla et al., 2009; Santos et al., 2010; Schulze et al., 2007; Shan et al., 2013; Siegel et al., 1984; Smith et al., 2010; Smith et al., 2013; Smucny et al., 2013; Song et al., 2014; Storozheva et al., 2016; Thoma et al., 2003; Thoma et al., 2008; Turetsky et al., 2009; Waldo et al., 1992; Waldo et al., 1988; Waldo et al., 1994; Waters et al., 2009; Williams et al., 2011; Wonodi et al., 2014; Yee et al., 1998; Yee et al., 2010; Zhang et al., 2012). Both study selection and data extraction were performed by two authors independently for both schizophrenia (IKA and MIA) and bipolar disorder (SZT and MIA), a third author (MHH) made final decisions for conflicts.
The ability of the brain to reduce the amount of trivial or redundant sensory inputs is called gating function. Dysfunction of sensory gating may lead to cognitive fragmentation and poor real-world functioning. The auditory dual-click paradigm is a pertinent neurophysiological measure of sensory gating function. This meta-analysis aimed to examine the subcomponents of abnormal P50 waveforms in bipolar disorder and schizophrenia to assess P50 sensory gating deficits and examine effects of diagnoses, illness states (first-episode psychosis vs. schizophrenia, remission vs. episodes in bipolar disorder), and treatment status (medication-free vs. medicated). Literature search of PubMed between Jan 1st 1980 and March 31st 2019 identified 2091 records for schizophrenia, 362 for bipolar disorder. 115 studies in schizophrenia (4932 patients), 16 in bipolar disorder (975 patients) and 10 in first-degree relatives (848 subjects) met the inclusion criteria. P50 sensory gating ratio (S2/S1) and S1–S2 difference were significantly altered in schizophrenia, bipolar disorder and their first-degree relatives. First-episode psychosis did not differ from schizophrenia, however episodes altered P50 sensory gating in bipolar disorder. Medications improve P50 sensory gating alterations in schizophrenia significantly and at trend level in bipolar disorder. Future studies should examine longitudinal course of P50 sensory gating in schizophrenia and bipolar disorder.
Striatal and Thalamic Auditory Response During Deep Brain Stimulation for Essential Tremor: Implications for Psychosis
2020, Neuromodulation
The P50, a positive auditory-evoked potential occurring 50 msec after an auditory click, has been characterized extensively with electroencephalography (EEG) to detect aberrant auditory electrophysiology in disorders like schizophrenia (SZ) where 61–74% have an auditory gating deficit. The P50 response occurs in primary auditory cortex and several thalamocortical regions. In rodents, the gated P50 response has been identified in the reticular thalamic nucleus (RT)—a deep brain structure traversed during deep brain stimulation (DBS) targeting of the ventral intermediate nucleus (VIM) of the thalamus to treat essential tremor (ET) allowing for interspecies comparison. The goal was to utilize the unique opportunity provided by DBS surgery for ET to map the P50 response in multiple deep brain structures in order to determine the utility of intraoperative P50 detection for facilitating DBS targeting of auditory responsive subterritories.
We developed a method to assess P50 response intraoperatively with local field potentials (LFP) using microelectrode recording during routine clinical electrophysiologic mapping for awake DBS surgery in seven ET patients. Recording sites were mapped into a common stereotactic space.
Forty significant P50 responses of 155 recordings mapped to the ventral thalamus, RT and CN head/body interface at similar rates of 22.7–26.7%. P50 response exhibited anatomic specificity based on distinct positions of centroids of positive and negative responses within brain regions and the fact that P50 response was not identified in the recordings from either the internal capsule or the dorsal thalamus.
Detection of P50 response intraoperatively may guide DBS targeting RT and subterritories within CN head/body interface—DBS targets with the potential to treat psychosis and shown to modulate schizophrenia-like aberrancies in mouse models.
P50 inhibitory sensory gating in schizophrenia: analysis of recent studies
2020, Schizophrenia Research
Inhibitory sensory gating of the P50 cerebral evoked potential to paired auditory stimuli (S1, S2) is a widely used paradigm for the study of schizophrenia and related conditions. Its use to measure genetic, treatment, and developmental effects requires a metric with more stable properties than the simple ratio of the paired responses.
This study assessed the ratio P50_S2μV/P50_S1μV and P50_S2μV co-varied for P50_S1μV in all 27 independent published studies that compared schizophrenia patients with healthy controls from 2000 to 2019. The largest study from each research group was selected. The Colorado research group's studies were excluded to eliminate bias from the first report of the phenomenon.
Across the 27 studies encompassing 1179 schizophrenia patients and 1091 healthy controls, both P50_S2μV co-varied for P50_S1μV and P50_S2μV/P50_S1μV significantly separated the patients from the controls (both P < 0.0001). Effect size for P50_S2μV co-varied for P50_S1μV is d' = 1.23. The normal distribution of P50_S2μV co-varied for P50_S1μV detected influences of maternal inflammation and effects on behavior in a recent developmental study, an emerging use for the P50 inhibitory gating measure. P50_S2μV/P50_S1μV was not normally distributed. Results from two multi-site NIMH genetics collaborations also support the use of P50_S2μV as a biomarker.
Both methods detect an abnormality of cerebral inhibition in schizophrenia with high significance across multiple independent laboratories. The normal distribution of P50_S2μV co-varied for P50_S1μV makes it more suitable for studies of genetic, treatment, and other influences on the development and expression of inhibitory deficits in schizophrenia.

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Gating of auditory response in schizophrenics and normal controls: Effects of recording site and stimulation interval on the P50 wave

Abstract

Biol. Psychiatry

Biol. Psychiatry

Electroencephalogr. Clin. Neurophysiol.

Biol. Psychiatry

Brain Res.

Electroencephalogr. Clin. Neurophysiol.

Exp. Neurol.

Biol. Psychiatry

Biol. Psychiatry

Electroencephalogr. Clin. Neurophysiol.

Electroencephalogr. Clin. Neurophysiol.

Electroencephalogr. Clin. Neurophysiol.

Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating and schizophrenia

Biol. Psychiatry

Family diagnoses missed on a clinical inpatient service

Am. J. Psychiatry

Auditory sensory gating in hippocampal neurons: A model system in the rat

Biol. Psychiatry

Dementia Praecox or the Group of Schizophrenias

Regional erp/attention deficits in schizophrenia

Abstracts from Annual Meeting of the Society of Biological Psychiatry

Effect of antipsychotic medication: Speed of information processing in schizophrenic patients

Am. J. Psychiatry

Prestimulus effects on human startle reflex in normals and schizophrenics

Psychophysiology

Brain Electrical Potentials and Individual Psychological Differences

Unilateral Electroconvulsive Therapy

Acta Psychiatr. Scand.

The Inhibitory Pathways of the Central Nervous System

Neurophysiological studies of sensory gating in mania: Comparison with schizophrenia

Biol. Psychiatry