The effects of interstimulus interval on sensory gating and on preattentive auditory memory in the oddball paradigm: Can magnitude of the sensory gating affect preattentive auditory comparison process?

P50, and mismatch negativity (MMN) are components of event-related potentials (ERP) reflecting sensory gating and preattentive auditory memory, respectively. Interstimulus interval (ISI) is an important determinant of the amplitudes of these components and N1. In the present study the interrelation between stimulus gating and preattentive auditory sensory memory were investigated as a function of ISI in 1.5, 2.5 and 3.5 s in 15 healthy volunteered participants. ISI factor affected the N1 peak amplitude significantly. MMN amplitude in 2.5 s ISI was significantly smaller compared to 1.5 and 3.5 s ISI. ISI X stimuli interaction on P50 amplitude was statistically significant. P50 amplitudes to deviant stimuli in 2.5 s ISI were larger than the P50 amplitudes in other ISIs. P50 difference (P50d) waveform amplitude correlated significantly with MMN amplitude. The results suggest that: (i) auditory sensory gating could affect preattentive auditory sensory memory by supplying input to the comparator mechanism; (ii) 2.5 s ISI is important in displaying the sensory gating and preattentive auditory sensory memory relation.     

N1 and the mismatch negativity are spatiotemporally distinct ERP components: disruption of immediate memory by auditory distraction can be related to N1

Event-related potentials (ERPs) were recorded for ignored tones presented during the retention interval of a delayed serial recall task. The mismatch negativity (MMN) and N1 ERP components were measured to discern spatiotemporal and functional properties of their generation. A nine-token sequence with nine different tone pitches was more disruptive than an oddball (two-token) sequence, yet this oddball sequence was no more disruptive than a single repeating tone (one-token). Tones of the nine-token sequence elicited augmented N1 amplitudes compared to identical tones delivered in the one-token sequence, yet deviants elicited an additional component (MMN) with distinct temporal properties and topography. These results suggested that MMN and N1 are separate, functionally distinct components. Implications are discussed for the N1 hypothesis and the changing-state hypothesis of the disruption of serial recall performance by auditory distraction.     

Sensory gating impairment associated with schizophrenia persists into REM sleep

Physiological measures of sensory gating are increasingly used to study biological factors associated with attentional dysfunction in psychiatric and neurologic patient populations. The present study was designed to assess sensory gating during rapid eye movement (REM) sleep in patients with schizophrenia, a population bearing a genetic load for gating impairment. Auditory event-related potentials (ERPs) were recorded in response to paired clicks during separate waking and overnight sleep recording sessions in controls and schizophrenia patients. Suppression of ERP component P50 was significantly impaired in the patient group during both waking and REM sleep, whereas the difference between groups for N100 gating was dependent on state. These results suggest that REM sleep is an appropriate state during which to assess P50 gating in order to disentangle the effects of state and trait on sensory gating impairment in other clinical populations.     

P50 and acoustic startle gating are not related in healthy participants

Although P50 event-related potential (ERP) suppression and acoustic startle prepulse inhibition are conceptualized as measures of sensory and sensorimotor gating, respectively, the relationship between these measures is unclear. In the present study, P50 and prepulse inhibition trials were interleaved in a single testing session to determine their relationship. Thirty-one healthy participants were presented with startle- and P50-eliciting stimuli across six trial blocks. Lead stimuli (i.e., the prepulse to the acoustic startle and the first click in the dual click ERP paradigm) resulted in significant gating, or amplitude attenuation, of responses to the startle probe and second paired click. There were no meaningful correlations between the P50 and prepulse inhibition variables, indicating that P50 suppression and acoustic startle prepulse inhibition measure distinct neural mechanisms. The implications of these findings for operationally defining the psychological construct of gating with these psychophysiological measures are discussed.     

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 (1 kHz, 75 dB, 50 ms, 5 ms rise/fall times, 330 ms SOA), separated by a 750 ms inter-trial interval. For MMN, the same tones were presented, with occasional pitch (1.2 kHz, 10%) or duration deviants (100 ms, 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.     

Sensory suppression effects to self‐initiated sounds reflect the attenuation of the unspecific N1 component of the auditory ERP

The suppression of the auditory N1 event‐related potential (ERP) to self‐initiated sounds became a popular tool to tap into sensory‐specific forward modeling. It is assumed that processing in the auditory cortex is attenuated due to a match between sensory stimulation and a specific sensory prediction afforded by a forward model of the motor command. The present study shows that N1 suppression was dramatically increased with long (～3 s) stimulus onset asynchronies (SOA), whereas P2 suppression was equal in all SOA conditions (0.8, 1.6, 3.2 s). Thus, the P2 was found to be more sensitive to self‐initiation effects than the N1 with short SOAs. Moreover, only the unspecific but not the sensory‐specific N1 components were suppressed for self‐initiated sounds suggesting that N1‐suppression effects mainly reflect an attenuated orienting response. We argue that the N1‐suppression effect is a rather indirect measure of sensory‐specific forward models.     

Consistency of abnormal sensory gating in first‐admission and chronic schizophrenia across quantification methods

The auditory P50/M50 ERP/event‐related field is subject to sensory gating, with partial suppression of the amplitude of the second of two (S1 and S2) clicks presented 500 ms apart. Schizophrenia patients have less gating, although quantification methods and associated effect sizes vary across studies using first‐admission and/or using chronic patients. The present study evaluated the impact of several methods of quantifying gating in first‐admission (FA) and chronic (CHR) schizophrenia patients and in healthy controls (HC). Magnetoencephalogram was measured in 35 FA, 58 CHR, and 28 HC during a paired‐click protocol. Sensory gating was quantified on sensor and source levels as a ratio (S2/S1) and as a S1‐minus‐S2 difference, with M50 amplitude scored relative to baseline and relative to M100 and to M40. Independent of quantification method, patients showed less sensory gating than HC, with medium‐to‐large effect sizes, without differences between FA and CHR. Results indicate that the frequently reported sensory gating deficit in schizophrenia is robust to variations in quantification methods and stage of disorder.     

Genetic overlap between P300, P50, and duration mismatch negativity.

Mismatch Negativity (MMN), P300, and P50 suppression event-related potential (ERP) components measure intermediate stages of information processing but little is known of how they relate to each other genetically. The present study used multivariate genetic model fitting analytic techniques in 46 monozygotic and 32 dizygotic twin pairs. P300, P50 suppression, and MMN were recorded using a 19-channel electroencephalograph (EEG). Zygosity was determined using DNA genotyping. Little evidence for either genetic or environmental association between each of the three ERP paradigms was found. This result suggests that P300, MMN, and P50 suppression serve to evaluate different brain information processing functions that may be mediated by distinct neurobiological mechanisms which in turn are influenced by different sets of genes. Within paradigm, P300 amplitude and latency shared about half of their genetic effects.     

Effects of sleep deprivation on auditory change detection: a N1-Mismatch Negativity study

The effects of sleep deprivation on neural activity underlying stimulus change detection are still debated. The aim of this study was to investigate the effects of sleep deprivation on the relationship between N1 refractoriness and Mismatch Negativity (MMN) as indexes of different stages of change detection. Respectively, N1 represents the sensory feature trace creation with stimulus repetition and MMN represents the memory-based detection of deviance in a new incoming stimulus. Event-related potentials (ERPs) were recorded from 22 healthy participants during a passive auditory oddball task after a night of normal sleep and after a night of total sleep deprivation (TSD). Importantly, stimulus presentation was organized as a train of 10 stimuli, so that N1 refractoriness could be measured as amplitude decrease with stimulus repetition within each train. Results showed that N1 refractoriness and MMN were not affected by TSD suggesting that the change detection process was preserved in our paradigm. However, the overall N1 amplitude increased after TSD, an effect that may be related to an enhancement of cortical excitability.     

Electrophysiological evidence for the hierarchical organization of auditory change detection in the human brain

Auditory change detection has been associated with mismatch negativity (MMN), an event‐related potential (ERP) occurring at 100–250 ms after the onset of an acoustic change. Yet, single‐unit recordings in animals suggest much faster novelty‐specific responses in the auditory system. To investigate change detection in a corresponding early time range in humans, we measured the Middle Latency Response (MLR) and MMN during a controlled frequency oddball paradigm. In addition to MMN, an early effect of change detection was observed at about 40 ms after change onset reflected in an enhancement of the Nb component of the MLR. Both MMN and the Nb effect were shown to be free from confounding influences such as differences in refractoriness. This finding implies that early change detection processes exist in humans upstream of MMN generation, which supports the emerging view of a hierarchical organization of change detection expanding along multiple levels of the auditory pathway.     

Mismatch negativity to auditory stimulus change recorded directly from the human temporal cortex

Mismatch negativity (MMN) is an event-related potential (ERP) component elicited by any discernible change in a repetitive sound even in the absence of attention. Previous studies have established that MMN is generated by change detection in a process comparing the deviant sensory input with the neural memory trace encoding the physical features of the repetitive sound. In the present study, we recorded MMNs to tonal frequency changes directly from the human temporal cortex of patients with electrodes implanted in the brain for diagnosis and therapy. The intracranially recorded MMN was found to be attention independent and modality specific. It was confined to a rather small area in temporal cortex, which was different from the structures where attention-dependent N2 and P3 responses to the frequency change could be recorded.     

Matching analysis of event related potentials in patients with bipolar disorder

The present paper is to investigate the variation characteristics and clinical application of event related potentials (ERPs) in patients with bipolar disorder. A total of 70 patients with bipolar disorder, with 39 patients in manic phase and 31 patients in depressive phase, and 50 health volunteers were recruited in the case-control study. The ERPs, such as P300, MMN, CNV, P50, were recorded by the Nihon Kohden evoked potential instrument. Compared with the healthy volunteers' latency in the control group, the latency of MMN, CNV, N2, P3a, P3b was longer in the manic phase group; the latency of MMN, CNV, P3a and P3b were longer and the amplitude of CNV was lower in the depressive phase group. The S2/S1 value of P50 obviously increased among the manic phase patients. With manic phase or depression phase of bipolar disorder, the variation characteristics of ERPs were different. The features of ERP reflect the cognitive dysfunction and sensory gating impairment of patient's brain. The results provide neural electrophysiological basis for clinical diagnosis and therapy of bipolar disorder.     

Heritability and Reliability of P300, P50 and Duration Mismatch Negativity

Background Event-related potentials (ERPs) have been suggested as possible endophenotypes of schizophrenia. We investigated the test–retest reliabilities and heritabilities of three ERP components in healthy monozygotic and dizygotic twin pairs.Methods ERP components (P300, P50 and MMN) were recorded using a 19-channel electroencephalogram (EEG) in 40 healthy monozygotic twin pairs, 19 of them on two separate occasions, and 30 dizygotic twin pairs. Zygosity was determined using DNA genotyping.Results High reliabilities were found for the P300 amplitude and its latency, MMN amplitude, and P50 suppression ratio components. Intra-class correlation (ICC) = 0.86 and 0.88 for the P300 amplitude and P300 latency respectively. Reliability of MMN peak amplitude and mean amplitude were 0.67 and 0.66 respectively. P50 T/C ratio reliability was 0.66. Model fitting analyses indicated a substantial heritability or familial component of variance for these ERP measures. Heritability estimates were 63 and 68% for MMN peak amplitude and mean amplitude respectively. For P50 T/C ratio, 68% heritability was estimated. P300 amplitude heritability was estimated at 69%, and while a significant familiality effect was found for P300 latency there was insufficient power to distinguish between shared environment and genetic factors.Conclusions The high reliability and heritability of the P300 amplitude, MMN amplitude, and P50 suppression ratio components supports their use as candidate endophenotypes for psychiatric research.Edited by Wendy SlutskeThis study was supported by British Academy grant SG-36241 to UE and the Stanley Medical Research Institute. Mei Hua Hall is awarded the Taiwanese scholarship at King’s College London. Katja Schulze is supported by a Guy’s & St Thomas’ Charitable Foundation Research Studentship. Elvira Bramon and Marco Picchioni are Wellcome Trust fellows.     

Cortical correlates of auditory sensory gating: A simultaneous near-infrared spectroscopy event-related potential study

Sensory gating refers to the ability of cerebral networks to inhibit responding to irrelevant environmental stimuli, a mechanism that protects the brain from information overflow. The reduction of the P50 amplitude (an early component of the event-related potential/ERP in electrophysiological recordings) after repeated occurrence of a particular acoustic stimulus is one means to quantitatively assess gating mechanisms. Even though P50 suppression has been extensively investigated, neuroimaging studies on the cortical correlates of auditory sensory gating are so far very sparse. Near-infrared spectroscopy (NIRS) is an optical imaging technique perfectly suitable for the investigation of auditory paradigms, since it involves virtually no noise. We conducted a simultaneous NIRS-ERP measurement to assess cortical correlates of auditory sensory gating in humans. The multi-channel NIRS recording indicated a specific activation of prefrontal and temporo-parietal cortices during conditions of increased sensory gating (dual-click trials). Combining the hemodynamic data with an electrophysiological index of the “gating quality” (gating quotient Q) revealed a positive correlation between the amount of sensory gating and the strength of the hemodynamic response during dual-clicks in the left prefrontal and temporal cortices. The results are in line with previous findings and confirm a possible inhibitory influence of the prefrontal cortex on primary auditory cortices.     

Combining electrophysiological and hemodynamic measures of the auditory oddball

The neural mechanisms of deviancy and target detection were investigated by combining high density event-related potential (ERP) recordings with functional magnetic resonance imaging (fMRI). ERP and fMRI responses were recorded using the same paradigm and the same subjects. Unattended deviants elicited a mismatch negativity (MMN) in the ERP. In the fMRI data, activations of transverse/superior temporal gyri bilateral were found. Attended deviants generated an MMN followed by an N2/P3b complex. For this condition, fMRI activations in both superior temporal gyri and the neostriatum were found. These activations were taken as neuroanatomical constraints for the localization of equivalent current dipoles. Inverse solutions for dipole orientation provide evidence for significant activation close to Heschl's gyri during deviancy processing in the 110-160-ms time interval (MMN), whereas target detection could be modeled by two dipoles in the superior temporal gyrus between 320 and 380 ms.     

Improved test-retest reliability of 50-ms paired-click auditory gating using magnetoencephalography source modeling

Used to study filtering abnormalities in schizophrenia, the paired-click paradigm suffers from poor test-retest reliability of the gating ratio, calculated from the P50 component of the ERP recorded at Cz approximately 50 ms following each of two stimuli. This study sought to improve reliability by assessing 50-ms gating at primary auditory cortices (PAC), the main generators of the P50 Cz component. MEG source modeling was used, taking advantage of the tangentially oriented PAC sources. Ten healthy subjects underwent three sessions, during which Cz-based and PAC-derived gating was measured. Unlike Cz P50, gating ratios at bilateral PACs achieved an intraclass coefficient of .8 or greater. Variability of gating within the same subject was also significantly smaller for bilateral PACs than for Cz P50. Paired-click gating ratio reliability can be improved by examining the individual PACs rather than composite scalp-recorded activity.     

A novel electrophysiological model of chemotherapy-induced cognitive impairments in mice

PURPOSE: Chemotherapeutic agents are known to produce persistent cognitive deficits in cancer patients. However, little progress has been made in developing animal models to explore underlying mechanisms and potential therapeutic interventions. We report an electrophysiological model of chemotherapy-induced cognitive deficits using a sensory gating paradigm, to correspond with performance in two behavioral tasks. EXPERIMENTAL DESIGN: Mice received four weekly injections of methotrexate and 5-fluorouracil. Whole-brain event-related potentials (ERPs) were recorded throughout using a paired-click paradigm. Mice underwent contextual fear conditioning (CFC) and novel-object recognition testing (NOR). RESULTS: Chemotherapy-treated animals showed significantly impaired gating 5 weeks after drug treatments began, as measured by the ratio of the first positive peak in the ERP (P1) minus the first negative peak (N1) between first and second auditory stimuli. There was no effect of drug on the amplitude of P1-N1 or latency of P1. The drug-treated animals also showed significantly increased freezing during fear conditioning and increased exploration without memory impairment during novel object recognition. CONCLUSIONS: Chemotherapy causes decreased ability to gate incoming auditory stimuli, which may underlie associated cognitive impairments. These gating deficits were associated with a hyperactive response to fear conditioning and reduced adaptation to novel objects, suggesting an additional component of emotional dysregulation. However, amplitudes and latencies of ERP components were unaffected, as was NOR performance, highlighting the subtle nature of these deficits.     

Mismatch Negativity Outside Strong Attentional Focus: A Commentary on Woldorff et al. (1991)

Several previous papers have suggested that the mismatch negativity (MMN), an event-related potential (ERP) component specific to stimulus change after repetition, is fully automatic, that is, not affected by attention. Woldorff, Hackley, and Hillyard (1991), however, report that the MMN elicited by an intensity decrement of a repeating stimulus is considerably attenuated when attention is strongly focused on other stimuli. The present commentary attributes most of this effect to attention effects on ERP components other than the MMN but also admits that some attentional reduction of the MMN component indeed occurred. This attenuation was interpreted by Woldorff et al. as indicating suppression of early sensory processing in unattended channels, but this is contraindicated by some very recent data from the present author's laboratory and elsewhere showing that the MMN to frequency change is not attenuated outside a strong attentional focus. Consequently, an alternative explanation is proposed for Woldorff et al.'s important finding.     

Genetic overlap between bipolar illness and event-related potentials

BACKGROUND: Electrophysiological endophenotypes are far less explored in bipolar disorder as compared to schizophrenia. No previous twin study of event-related potentials (ERPs) in bipolar illness has been reported. This study uses a twin design and advanced genetic model fitting analyses aiming to (1) assess and quantify the relationship of a range of ERP components with bipolar disorder with psychotic features, and (2) examine the source of the relationship (due to genetic or environmental factors). METHOD: P300, P50 suppression and mismatch negativity (MMN) were recorded in 10 discordant monozygotic (MZ) bipolar twin pairs, six concordant MZ bipolar twin pairs and 78 control twin pairs. Statistical analyses were based on structural equation modelling. RESULTS: Bipolar disorder was significantly associated with smaller P300 amplitude and decreased P50 suppression. Genetic correlations were the main source of the associations, estimated to be -0 x 33 for P300 amplitude and 0 x 46 for P50 ratio. Individual-specific environmental influences were not significant. MMN and P300 latency were not associated with the illness. CONCLUSIONS: The results provide supporting evidence that P300 amplitude and P50 suppression ratio are ERP endophenotypes for bipolar disorder.     

Event-related potentials associated with sound discrimination versus novelty detection in children

In children, deviant sounds in an oddball paradigm elicit a mismatch negativity (MMN) indexing discrimination of sound change and late difference negativity (LDN) with unknown functional significance. Salient sounds elicit an ERP index if orienting, P3a, and a late negative component, Nc. We compared children's responses elicited by moderate sound changes and novel sounds to examine the relationships between MMN and LDN, and LDN and Nc. Two components of the Nc, the Nc1 and Nc2, were identified. The scalp topography of LDN differed from those of the MMN and Nc1. Children's early P3a appeared mature but late P3a lacked frontal predominance. The findings suggested that LDN is not linked with either the sensory or attentional processing. It might reflect cognitive, albeit preattentive, processing of sound change. The Nc1 appears to reflect cognitive attentive processing of salient stimuli and the Nc2 might reflect reorienting after distraction.