Dieter Zerbin

Auditory event-related potentials (ERPs) and mismatch negativity (MMN) in healthy children and those with attention-deficit or tourette/tic symptoms

The study compares 5 auditory event-related potential (ERP) components (P1 to P3) after 3 tones differing in pitch and rarity, and contrasts the mismatch negativity (MMN) between them in 12 children with attention-deficit hyperactivity disorder (ADHD; mean 10.2 years of age), 12 healthy controls pairwise matched for age (controls), and 10 with Chronic Tic or Tourette Syndrome (TS). Topographic recordings were derived from 19 scalp electrodes. Four major effects are reported. (a) Shorter latencies in ADHD patients were evident as early as 100 ms. (b) Both ADHD and TS groups showed very large P2 components where the maxima were shifted anteriorly. The differences in the later potentials were of a topographical nature. (c) Frontal MMN was non-significantly larger in the ADHD group but normalized data showed a left rather than a right frontal bias as in control subjects. Maxima for TS were usually posterior. (d) ADHD patients did not show the usual right-biased P3 asymmetry nor the frontal versus parietal P3 latency difference. From these results it is suggested that ADHD patients process perceptual information faster from an early stage (N1). Further, along with the TS group, ADHD patients showed an unusually marked inhibitory phase in processing (P2), interpreted as a reduction of the normal controls on further processing. Later indices of stimulus processing (N2-P3) showed a frontal impairment in TS and a right hemisphere impairment in ADHD patients. These are interpreted in terms of the difficulties in sustaining attention experienced by both ADHD and TS patients.

Impaired attention-dependent augmentation of MMN in nonparanoid vs paranoid schizophrenic patients: A comparison with obsessive-compulsive disorder and healthy subjects

Mismatch negativity (MMN), in the deviant-minus-standard event-related potential (ERP) difference-waveform, may represent a working memory trace of the tone difference. Most but not all studies find MMN reduced in schizophrenic patients. This report investigates if differences may be attributable to experimental condition (diffuse vs focused attention), component identification (N1-like vs N2-like), topographic distribution, and clinical condition (with/without paranoid-hallucinatory symptoms, PH/NP). Comparisons were made for 12 PH, 12 NP schizophrenic patients with 13 obsessive compulsive and 25 normal control subjects. Frontal MMN reduction in schizophrenics largely resulted from an absence of an increase in focused attention conditions as in comparison groups. But there was a marked temporal activity locus in NP patients. These features were not reflected in other components except for a visible but nonsignificant N1-like temporal locus in NP patients. Further, schizophrenic patients did not show an increase in late positivity with focused attention like the comparison groups. The results show that so-called automatic processing deficits (amount and locus of MMN) are best seen in situations requiring the activation of controlled attentional processes. It is suggested that impaired processing of irrelevant stimuli and reduced frontal MMN in NP patients may reflect reduced dopaminergic responsivity.

Event-related potentials during an auditory discrimination with prepulse inhibition in patients with schizophrenia, obsessive-compulsive disorder and healthy subjects.

Prepulse inhibition (PPI) is a measure of the influence of a stimulus (S1) on the response elicited by a second stimulus (S2) occurring shortly afterwards. Most S1/S2 measures of gating have used behavioural startle and the P50 event-related potential (ERP) amplitudes to detect PPI in a simple paired stimulus paradigm. We report on two behavioural (reaction time, RT, and the electromyographically recorded response of the musculus orbicularis oculi, EMG) and 5 ERP measures of PPI where S2 was the target in an auditory two-tone discrimination. Subjects were 21 healthy controls (CON), 11 obsessive-compulsive (OCD) and 9 schizophrenic patients (SCH). The prepulse 100 ms before S2 induced more omission errors and longer RTs compared to 500ms S1-S2 interval in all subjects. PPI was also evident in EMG, P50, N1, P3 but not P2 or N2 amplitudes of CON subjects. SCH patients showed attenuation of PPI on the same measures. OCD patients were characterized only by their slow RT and a marginal attenuation of PPI of the EMG response. A correlational analysis implied separate relationships of ERP indices of PPI to the cognitive and psychomotor consequences of the prepulse on behavioural and discrimination responses. However, SCH patients showed a general rather than a specific impairment of these indices.

Auditory event-related potential (ERP) and difference-wave topography in schizophrenic patients with/without active hallucinations and delusions: a comparison with young obsessive-compulsive disorder (OCD) and healthy subjects

Event-related potentials (ERPS) in schizophrenics have been reported to show a reduced P3 on the left and less frontal mismatch negativity (MMN). But the specificity of such findings to component, its locus, the type of eliciting event and patient group remains uncertain. Hence, we examined ERP topography for P3, N2 and 3 precursor peaks according to stimulus (3-tone oddball), attention condition (diffuse/focused) and four types of difference-waves. We contrasted 24 healthy and 13 OCD subjects with schizophrenic patients with high versus low ratings of active delusions and hallucinations (12 paranoid-hallucinatory, PH; 12 nonparanoid, NP). P3 peaks were delayed and reduced in NP and PH groups. Midline peaks were usual in focused attention and a right bias in diffuse attention. P3 responses to irrelevant standards remained lateral in NP and small in OCD patients. All showed a small left and anterior bias in the P3-like peak in difference-waves. Mismatch negativity waveform (MMN) peaks shifted to the right in OCD, to both sides in PH and posteriorly in NP patients. Frontal processing negativity was biased to the left (early) in NP and to the right (late) in PH groups. Early peak topography reflected some later changes (e.g. PH and NP groups; P1-like peak, right bias absent; N1-like peak depressed and widely distributed; NP group, P2-like peak smaller on the left). In OCD patients, peak latencies were topographically undifferentiated (P1, P2) or delayed (N2). The OCD group showed an unusual regional allocation of processing effort. Before 200 ms frontocentral activity was more widespread in Ph and NP groups. Lateralization of negativity in target- and nontarget-derived difference-waves may reflect differential disruption of the frontal-temporal dialogue in registering important vs unimportant features. NP patients, in particular, treated irrelevant stimuli anomalously.

The topography of event-related potentials in passive and active conditions of a 3-tone auditory oddball test

Normalized event-related potential (ERP) data were analysed for topographical differences of ERP amplitude or latency in two conditions of a 3-tone oddball paradigm. The aim was to compare perception-related features relating to tone-type (passive non-task condition) with focussed attention-related features (active discrimination of target from non-target) in 5 ERP components from 23 young healthy subjects. The tones used were a common standard (70%, 0.8 KHz), a deviant standard (15%, 2 KHz) and a 1.4 KHz tone (15%, t) also used as the target (T). A site x tone interaction was obtained for P1 amplitude (augmenting with pitch anterior to posterior). The opposite tendency was seen for P2 to the right of midline maxima. No interaction was obtained for N1 amplitude. Condition became relevant for the N2-P3 complex. Frontal N2 amplitude increased after rare tones in the active condition. Posterior P3 peak size distinguished between tone (more widespread response to the common tone) and condition (more right-sided in the passive condition). The common tone elicited more widespread shift to the right than the rare tones. Latency was affected by condition from the P2 onwards and confirmed many of the amplitude interactions. This report extends and qualifies well-known main effects of tone and condition through main site effects to lateral sites. It supports claims of multiple sources of ERP components, except for N1 and P2. The contributions of these sources are influenced by tone-features (from P1) and the presence or absence of focussed attention (from the N2-P3 complex).

A topographic event-related potential follow-up study on `prepulse inhibition' in first and second episode patients with schizophrenia

Dopamine agonists impair and antagonists normalize prepulse inhibition (PPI) of startle and gating of the P50 event-related potential (ERP), but the within-subject effect of treatment on impaired gating in schizophrenia has not been studied. We report the first results of a longitudinal study using PPI of ERPs as a measure of sensory gating in an auditory Go/NoGo discrimination. After admission and approximately 3 months later, at discharge, 15 patients with schizophrenia performed a discrimination between a 1.4 kHz target tone and an 0.8 kHz non-target tone with no prepulse, or with a prepulse at 100 ms or 500 ms before either tone. ERPs were recorded from 19 sites. Healthy subjects were studied twice, with 3 months between sessions. PPI of the P50 peak in the 100-ms condition was reduced in patients on admission. At discharge, decreased negative symptoms correlated with enhanced P50-PPI at frontocentral sites. After treatment increased N100-PPI at centrotemporal sites correlated with fewer positive symptoms. At frontal sites in the 100-ms condition, the initially small difference of non-target minus target P300 amplitudes increased as negative symptoms decreased. It is concluded that weak auditory prepulses interfere with early auditory stimulus processing (P50), channel selection (N100) and selective attention (P300). Gating of these stages of processing is impaired in psychotic patients and treatment tends to normalize gating in tandem with improvements of different types of symptoms.

Auditory target processing in methadone substituted opiate addicts: The effect of nicotine in controls

BackgroundThe P300 component of the auditory evoked potential is an indicator of attention dependent target processing. Only a few studies have assessed cognitive function in substituted opiate addicts by means of evoked potential recordings. In addition, P300 data suggest that chronic nicotine use reduces P300 amplitudes. While nicotine and opiate effects combine in addicted subjects, here we investigated the P300 component of the auditory event related potential in methadone substituted opiate addicts with and without concomitant non-opioid drug use in comparison to a group of control subjects with and without nicotine consumption.MethodsWe assessed 47 opiate addicted out-patients under current methadone substitution and 65 control subjects matched for age and gender in an 2-stimulus auditory oddball paradigm. Patients were grouped for those with and without additional non-opioid drug use and controls were grouped for current nicotine use. P300 amplitude and latency data were analyzed at electrodes Fz, Cz and Pz.ResultsPatients and controls did not differ with regard to P300 amplitudes and latencies when whole groups were compared. Subgroup analyses revealed significantly reduced P300 amplitudes in controls with nicotine use when compared to those without. P300 amplitudes of methadone substituted opiate addicts were in between the two control groups and did not differ with regard to additional non-opioid use. Controls with nicotine had lower P300 amplitudes when compared to patients with concomitant non-opioid drugs. No P300 latency effects were found.ConclusionAttention dependent target processing as indexed by the P300 component amplitudes and latencies is not reduced in methadone substituted opiate addicts when compared to controls. The effect of nicotine on P300 amplitudes in healthy subjects exceeds the effects of long term opioid addiction under methadone substitution.

The Topography of 4 Subtraction Erp-Waveforms Derived from a 3-Tone Auditory Oddball Task in Healthy Young Adults

Five components were studied in 4 subtraction waveforms derived from ERPs obtained in passive and active conditions of a 3-tone oddball task (common = 70%, C, 0.8 KHz; deviant = 15%, D, 2 KHz; 1.4 KHz = 15%, t, also used as a target (T)). These waveforms reflect different stimulus-mismatch processes and thus their topography could be revealing of different brain regions mediating them. The following mismatches were studied: stimulus-mismatch (deviant--common, D/C, rarity and pitch confounded), pitch-mismatch (T--deviant, T/D, rarity not target features controlled), attention-mismatch (T-t), T/t, controlled for pitch and rarity to show the influence of target features). These are compared with Goodins procedure [G-wv, (T--common (active))--(t--common (passive))]. There were main site effects in normalized data in all cases (not P2 and N2 latency). There were separate frontal and posterior contributions to P1, with the former emphasized where target comparisons were involved. Frontal N1 peaks, largest in D/C, spread posterior and to the right where target matching was involved. P2 posterior maxima were also less localized where target features were involved in the comparison. N2 topography was similar between waveforms but spread slightly more to each side in the T/t comparison. Onset was earlier in the D/C comparison. Parietal P3 peaks in waves based on target-ERPs showed a left temporal shift (vs D/C), though in T/D P3 was in fact maximal on the right. Thus an attentional effect is evident as early as 60 ms. Target features modify the anteroposterior distribution of positivity and negativity for the early components and in the lateralization of P3-like positivity. A comparison of waveforms by latency of potential shift (running t-test) vs peak identification (MANOVA) is illustrated and discussed. D/C and T/t (rather than T/D or G-wv) waveforms are recommended for distinguishing comparator mechanisms for stimulus- and task-relevant features.

Signs of differential stimulus processing problems: a comment on event-related potentials in young schizophrenic and autistic subjects.

A comparison of the Nd (negative difference ERP) in a 3-tone auditory oddball paradigm (task-minus-nontask conditions) for a 16 y-old healthy adolescent with a 16y-old patient with paranoid schizophrenia. Early (100-200 ms) and late Nd components (200-300 ms) were reduced in amplitude and shifted in topography centromedially in the patient. While we have recorded a similar impairment in schizoaffective patients, this problem was not evident in disorganised schizophrenia or OCD. Indeed, no impairment of Nd amplitude was observed in a comparison of 7 healthy children with 7 patients with childhood autism.

Prepulse-Inhibition-Defizite in der akustischen Signalverarbeitung bei jungen schizophrenen Patienten

Zwei grundlegende experimentelle Verfahren zeigen, das sich schizophrene Patienten bereits auf einer sehr fruhen Stufe ihrer Informationsverarbeitung von gesunden Probanden unterscheiden: Erstens, die Inhibition des P50-Anteils des akustisch evozierten Potentials ist nur ineffektiv konditionierbar [3], und zweitens, der akustische Startie-Reflex last sich durch einen leisen Vorimpuls weniger ausgepragt hemmen als bei gesunden Vergleichsprobanden [2] (Abb. 1).