Novelty-elicited mismatch negativity in patients with schizophrenia on admission and discharge.

OBJECTIVE: Given recent reports of differences between mismatch negativity (MMN) elicited by always novel sounds (novelty-elicited MMN) and that elicited by repeated rare deviants (conventional MMN), we investigated novelty-elicited MMN and P3a in patients with schizophrenia before and after a nonstandardized inpatient treatment. DESIGN: Electrophysiological and clinical assessment of patients on admission and discharge from hospital. Assessment of control subjects on 2 sessions. SETTING: Inpatient treatment in a psychiatric university hospital. SUBJECTS: 20 patients with schizophrenia and 21 healthy control subjects of similar age and sex. Selection of patients with first- to third-episode schizophrenia. OUTCOME MEASURES: Early and late component MMN amplitudes and latencies, P3a amplitudes and latencies, Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), Extrapyramidal Symptom Scale (EPS), Abnormal Involuntary Movement Scale (AIMS) and chlorpromazine equivalents. RESULTS: In patients with schizophrenia, novelty-elicited MMN was unimpaired on admission, and there was a statistically significant reduction of the late MMN component with treatment. Improvements in symptom expression were associated with increased latencies of the early MMN component. CONCLUSION: Results indicate differences in information processing between conventional and novelty-elicited MMN. Some components of the novelty-elicited MMN might be more state dependent than those of the conventional MMN.

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.

Development and topography of auditory event-related potentials (ERPs): mismatch and processing negativity in individuals 8-22 years of age.

How do event-related potentials (ERPs) reflecting auditory processing develop across adolescence? Such development was described for five ERP components in four groups of 11 healthy participants with mean ages of 10, 14, 17, and 21 years. Data from 19 sites during diffuse (passive) and focused (discrimination) attention in a three-tone oddball were analyzed to see how ERP loci varied with age for tone type, attention condition, and for four types of difference waves reflecting nontarget and target comparisons. Age interacted with site for most components. P1 loci sensitive to rare tones moved posteriorly and N1 loci lost their right bias in early puberty. The P2 loci did not move anterior to Cz until adulthood. N2 amplitude, sensitive to attention condition, developed a frontal focus by 17 years. Right-biased P3 loci moved to the midline with focused attention similarly in all age groups. Difference waves developed in three stages: In 10-year-old participants, early deflections (< 150 ms) were diffusely distributed; in midadolescent participants, the main frontal negative component (150-300 ms) became well formed and lost an earlier right bias; and for participants 17 years old and older, the late positive complex developed a right bias in target-derived waves. Latency decreases for early frontal components were marked in participants 10-14 years old and for later posterior components in participants 14-17 years old. Major developments appeared at the onset of adolescence in early stimulus selection processes and during adolescence in the differential use of this information (N2- and P3-like latencies).

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.

A left temporal lobe impairment of auditory information processing in schizophrenia: an event-related potential study.

A measure of auditory prepulse inhibition (PPI) is the reduction of the scalp-recorded P1 event-related potential (ERP) after a sound that is preceded by 100-300 ms by a click as prepulse. This measure of sensory gating was adapted to study the effect of a prepulse on processing tones that were part of a 'go no-go' discrimination. ERPs were recorded at right and left, frontal and temporal sites in groups of patients with schizophrenia (SCH) or obsessive compulsive disorder (OCD) and healthy controls (CON). A prepulse 100 ms but not 500 ms before either tone reduced the P1 ERP amplitude in healthy and OCD subjects but not SCH patients. At frontal and temporal recording sites the P1 amplitude was similar bilaterally in controls but showed a right temporal shift in the SCH patients. If the tone was the 'no-go' tone, the prepulse reduced the N1 amplitude in both the CON and SCH groups. The N1 was similar, bilaterally in controls but again showed a right temporal shift in the SCH group. These results show a reduction of a PPI-like effect on early processing (P1) that is more marked in the left hemisphere of SCH patients and may affect channel selection for processing information (N1) about task-relevant sounds.

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.

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.

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.

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).

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 Goodin's 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.

Negative difference (Nd), an ERP marker of stimulus relevance: different lateral asymmetries for paranoid and nonparanoid schizophrenics.

We studied Nd in psychotic patients with varying degrees of paranoid symptoms. Nd is an ERP measurement of the difference in the way a nonattended tone is registered and the way the same tone is registered when used later as a discrimination target. In a three-tone oddball paradigm with passive-tone presentation and active discrimination, we recorded from 19 sites in 22 young healthy subjects and 28 schizophrenics. Nd (200-260 ms) was bilaterally symmetrical in healthy subjects. Paranoid patients showed a left frontal/right temporoparietal amplitude reduction which was reversed in nonparanoid subjects (reduced at right frontal/left posterior sites). These asymmetries were clearer when the groups were separated according to active paranoid symptoms rather than by diagnosis. There would therefore seem to be functional asymmetries mediating stimulus relevance in schizophrenics which differ from controls and differ between patients with and without active paranoid symptoms.

Altered fronto-central PINV topography and the primary negative syndrome in schizophrenia.

Postimperative negative variation (PINV) was recorded during a warned reaction time paradigm in 16 chronic DSM-IIIR schizophrenics in remission. Clinical symptoms were assessed by BPRS, SANS and the anhedonia scale of the Chapman Questionnaire. Ten healthy controls were studied in the same manner. Over the fronto-central area we found a significantly elevated PINV amplitude with an altered topographical distribution in the patient group. The difference values 'PINV Cz-PINV Fz' were correlated negatively with primary negative symptoms of schizophrenia.

Postimperative negative variation and skin conductance response in chronic DSM-III-R schizophrenia.

The hypothesis was tested that there are relationships between schizophrenic negative or deficit symptoms, the skin conductance nonresponding and an elevated amplitude of the postimperative negative variation (PINV). These variables were recorded in 16 chronic schizophrenics and 10 healthy controls. Clinical symptoms were assessed by the Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Frankfurt Complaint Questionnaire 3 and Chapman Questionnaire. In the patient group we found a significantly elevated PINV at Fz. Surprisingly, only one patient was a skin conductance nonresponder. PINV amplitude at Fz and the number of skin conductance responses to habituation were not correlated with negative or deficit symptoms inclding anhedonia. The hypothesis thus had to be rejected.

[Event-related potentials in schizophrenic patients in the acute phase and in remission]. / Ereigniskorrelierte Potentiale bei schizophrenen Patienten im akuten Krankheitsschub und in Remission.

In 15 schizophrenic patients event-related potentials were recorded during an auditory two-tone-discrimination task in the acute phase and after remission. The control group consisted of ten healthy subjects of the same age. The schizophrenic patients showed reduced amplitudes of N1, P2 and P3 and prolonged latencies of N2 and P3 independent of neuroleptic medication and clinical state. We found no differences in the topographical distribution of P3 between schizophrenic patients and controls. The changes of the event-related potentials in the schizophrenic patients may be interpreted as electrophysiological correlates of basic disturbances in information processing in schizophrenia.

Auditory brainstem response (ABR) in congenital central alveolar hypoventilation.

Auditory brainstem responses (ABRs) were studied in a child with congenital central alveolar hypoventilation showing marked depression of respiratory drive during sleep. During wakefulness and normoventilation no ABR abnormalities were found, either at the age of 14 months or five years. ABR recordings during sleep at 14 months of age showed marked wave V latency and wave I to wave V interpeak latency prolongation of about 0.4 ms both for periods of hypoventilation and normoxic hypercapnia. ABR findings of this and other studies carried out in sleep apneas are discussed with respect to brainstem dysfunction associated with varied sleep apnea syndromes.

Evoked potential assessment of mental function during recovery from severe head injury.

Event-related potential recording and neuropsychologic testing were carried out on 18 severely head-injured patients and on a control group. At early stages of injury the patients had prolonged P3 latencies and reduced psychometric scores. In the assessment of individual patients the P3 latency proved to be a measure that diagnosed cognitive impairment with clinically acceptable levels of accurate classification. On retesting 4.6 +/- 1.6 months after trauma, normal values were found for the neuropsychologic measures and a residual latency prolongation for P3, indicating the P3 latency to be a sensitive index of subtle residual brain dysfunction due to head injury.

[Regulation of respiration during sleep in congenital central sleep apnea]. / Die Regulation der Atmung während des Schlafes bei kongenitaler zentraler Schlaf-Apnoe.

We report on 2 children aged 13 and 14 months with congenital central alveolar sleep apnea which showed depression of respiratory drive during sleep resulting from dysfunction of central chemoreceptors. Hypoventilation was found to be more severe during NREM sleep (minimum of alveolar ventilation in stages 3/4) than during REM sleep. During NREM sleep arousal responses to hypoxia proved to be an important factor in influencing the level of alveolar ventilation and in preventing fatal asphyxia.

[Event-related brain potentials and intellectual impairment--a study in patients with brain tumor and craniocerebral trauma]. / Ereigniskorrelierte Hirnpotentiale und intellektuelle Beeinträchtigung--Eine Untersuchung bei Patienten mit Hirntumor und Schädelhirntrauma.

Event-related potential recording (component N1, P2, N2, and P3) and neuropsychological assessment of cognitive impairment were carried out on 15 patients with brain tumour, 15 patients with severe head injury and 24 controls. The tumour and trauma patients had significantly lower psychological test scores, smaller N1 amplitudes and longer N2 and P3 latencies than normals. For the tumour and trauma patients significant correlations were found between N2 and P3 latency and the Mini-Mental State test and memory tests. For individual patients abnormally increased N2 and P3 latency was found to occur in association with abnormally reduced neuropsychological test scores. N2 and P3 latency proved the only electrophysiological variables examined which provided a measure of cerebral functioning correlating with the psychometric variables. N2 and P3 latency may be regarded as a useful diagnostic test for cognitive impairment especially in patients with motor handicaps, to whom neuropsychological tests cannot be administered.

Clinical application of event related potentials in patients with brain tumours and traumatic head injuries.

Event related potential recording and psychometric evaluation of cognitive impairment were carried out on 21 patients with brain tumours, 21 patients with severe head injuries and 24 controls. The tumour and trauma patients who met the psychometric inclusion criteria for dementia, but not the non-demented patients, had significantly longer N2 and P3 latencies than the controls. In assessing individual patients P3 latency correctly differentiated between demented and non-demented patients in 81% of cases (for N2 latency 77%). Particularly P3 latency may provide a practical and objective measure of mental impairment in neurosurgical disorders producing dementia. Marked asymmetry in N2 and P3 amplitudes between hemispheres was observed in a number of cases. No significant relationship was found between diminution of N2 and P3 components and side of lesion.