Alan T. Bates

Error-related negativity and correct response negativity in schizophrenia

OBJECTIVES To examine error-related negativity (ERN) and correct response negativity (CRN) in schizophrenia in light of two previous conflicting reports, and to determine their relation to disorganization, psychomotor poverty and reality distortion. METHODS Event-related potentials were recorded from 21 schizophrenic and 21 control participants who performed a simple go/no-go task. Response-locked potentials were computed for errors of commission and for correct-hits. Scores for reality distortion syndrome, psychomotor poverty syndrome and disorganization syndrome were determined for each schizophrenic participant using the Signs and Symptoms of Psychotic Illness (SSPI) scale. RESULTS ERN produced during error trials and CRN produced during correct trials were significantly larger in the control participant group than in the schizophrenic participant group. In the schizophrenic patients, ERN amplitude was negatively correlated with psychomotor poverty syndrome score and CRN amplitude was negatively correlated with disorganization syndrome score. CONCLUSIONS Decreased ERN and CRN in the schizophrenic participant group suggests abnormal internal behavior monitoring in schizophrenic patients. Patients with high disorganization symptoms may employ an abnormal strategy for comparing actual response outcome with desired response outcome, while patients with psychomotor poverty may be less emotionally responsive to errors.

Brain potentials implicate temporal lobe abnormalities in criminal psychopaths.

Psychopathy is associated with abnormalities in attention and orienting. However, few studies have examined the neural systems underlying these processes. To address this issue, the authors recorded event-related potentials (ERPs) while 80 incarcerated men, classified as psychopathic or nonpsychopathic via the Hare Psychopathy Checklist--Revised (R. D. Hare, 1991, 2003), completed an auditory oddball task. Consistent with hypotheses, processing of targets elicited larger frontocentral negativities (N550) in psychopaths than in nonpsychopaths. Psychopaths also showed an enlarged N2 and reduced P3 during target detection. Similar ERP modulations have been reported in patients with amygdala and temporal lobe damage. The data are interpreted as supporting the hypothesis that psychopathy may be related to dysfunction of the paralimbic system--a system that includes parts of the temporal and frontal lobes.

Cognitive deficits in early-onset schizophrenia spectrum patients and their non-psychotic siblings: A comparison with ADHD

BACKGROUND Previous research has shown cognitive deficits in patients with schizophrenia spectrum disorders in the areas of executive function, verbal memory and attention. Subtle deficits have been shown in healthy first-degree relatives of patients, suggesting that they may be trait markers. The specificity of these markers for schizophrenia compared with another neurodevelopmental disorder, Attention Deficit Hyperactivity Disorder (ADHD) has not been reliably established. METHODS The Rey Auditory Verbal Learning Test (RAVLT), Hayling Sentence Completion Test (HSCT), FAS Test of orthographic verbal fluency (FAS) and Continuous Performance Test-Identical Pairs (CPT-IP) were administered to adolescent schizophrenia spectrum patients (SZ; n=30), adolescent siblings of schizophrenia spectrum patients (SZ-SIB; n=36), healthy control participants (HC; n=72); a neurodevelopmental comparison group of adolescents with ADHD (n=27). RESULTS The SZ group were impaired on all measures. The SZ-SIB group were impaired on IQ, immediate recall (RAVLT), target sensitivity (CPT-IP), response initiation (HSCT); error rates for the FAS and HSCT. There were no significant differences between the SZ-SIB and ADHD groups on individual measures of cognitive function. Principal Components Analysis revealed four factors on which further analyses were conducted. The SZ-SIB and ADHD groups showed different profiles of impairment on components related to response initiation and sustained attention/vigilance when each was compared with the HC group. CONCLUSIONS Deficits in intellectual function, verbal memory and response initiation/inhibition were found in the SZ-SIB group indicating that these are markers of risk for schizophrenia. Subtle differences in profiles of impairment in the SZ-SIB and ADHD groups on composite measures of attention and response initiation require further investigation.

External Behavior Monitoring Mirrors Internal Behavior Monitoring

Abstract: The discovery of mirror neurons in monkeys has reshaped thinking about how the brain processes observed actions. There is growing evidence that these neurons, which show similar firing patterns for action execution and observation, also exist in humans. Many parts of the motor system required to perform a specific action are activated during the observation of the same action. We hypothesized that behavior monitoring that occurs during action execution is mirrored during action observation. To test this, we measured error negativity/error-related negativity (Ne/ERN) while participants performed and observed a Go/NoGo task. The Ne/ERN is an event-related potential that is thought to reflect an error detection process in the brain. In addition to finding an Ne/ERN for performed errors, we found that an Ne/ERN was also generated for observed errors. The Ne/ERN for observed errors may reflect a system that plays a key role in imitation and observational learning.

Low-frequency EEG oscillations associated with information processing in schizophrenia.

Numerous studies have described attenuated event-related potential (ERP) component amplitudes in schizophrenia (e.g., P300, Mismatch Negativity (MMN), Error Negativity/Error-Related Negativity (Ne/ERN)). Functional magnetic resonance imaging (fMRI) studies have typically shown decreased recruitment of diverse brain areas during performance of tasks that elicit the above ERP components. Recent research suggests that phase-resetting of slow-oscillations (e.g., in the delta and theta bands) underlies the potentials observed in ERP averages. Several studies have reported that slow-oscillations are increased in amplitude in people with schizophrenia at rest. Few studies have examined event-related low-frequency oscillations in schizophrenia. We examined event-related evoked and induced delta and theta activity in 17 people with schizophrenia and 17 healthy controls in two go/no-go task variants. We analyzed stimulus-related and response-related oscillations associated with correct-hits, correct-rejects and false-alarms. Our results reveal a pattern of reduced delta and theta activity for task-relevant events in schizophrenia. The findings indicate that while low-frequency oscillations are increased in amplitude at rest, they are not coordinated effectively in schizophrenia during various information processing tasks including target-detection, response-inhibition and error-detection. This slow-oscillation coordination abnormality may help explain the decreased recruitment of brain areas seen in fMRI studies.

Event-related potentials in adolescents with schizophrenia and their siblings: a comparison with attention-deficit/hyperactivity disorder.

BACKGROUND Identifying trait markers specific to schizophrenia might uncover mechanisms underlying illness susceptibility. Previous research shows the N2 and P3 event-related potentials are abnormal in schizophrenia; specificity of these potential trait markers has not been well established. METHODS Electroencephalogram data were recorded from four adolescent groups: early-onset schizophrenia patients (SZ; n = 30); non-psychotic siblings of schizophrenia patients (SZ-SIB; n = 36); healthy control subjects (HC; n = 36); a neurodevelopmental attention-deficit/hyperactivity disorder (ADHD) comparison group (n = 27), during auditory oddball and visual go/no-go tasks. The P3 was measured to targets in the oddball task. The N2 and P3 were measured to go and no-go stimuli in the go/no-go task. RESULTS Compared with the HC group, the SZ and SZ-SIB groups showed significantly reduced auditory oddball P3 amplitude. Visual P3 amplitude was significantly reduced in the SZ group for no-go stimuli and the SZ-SIB group for go and no-go stimuli. The P3 amplitude in the ADHD group was not significantly reduced for either paradigm. The SZ and ADHD groups showed significantly reduced N2 amplitude in the go/no-go task; the SZ-SIB group was not significantly different from the HC group. CONCLUSIONS Results revealed reduced P3 amplitude in schizophrenia patients and adolescent non-psychotic siblings in an auditory oddball and a visual go/no-go task. The SZ-SIB and ADHD groups showed a different ERP profile when each was compared with the HC group: siblings showed reduced P3 amplitude in both tasks and normal N2 in the go/no-go task; the opposite pattern was observed in the ADHD group.

Abnormal processing of speech during oddball target detection in schizophrenia

Healthy subjects show increased activation in left temporal lobe regions in response to speech sounds compared to complex nonspeech sounds. Abnormal lateralization of speech-processing regions in the temporal lobes has been posited to be a cardinal feature of schizophrenia. Event-related fMRI was used to test the hypothesis that schizophrenic patients would show an abnormal pattern of hemispheric lateralization when detecting speech compared with complex nonspeech sounds in an auditory oddball target-detection task. We predicted that differential activation for speech in the vicinity of the superior temporal sulcus would be greater in schizophrenic patients than in healthy subjects in the right hemisphere, but less in patients than in healthy subjects in the left hemisphere. Fourteen patients with schizophrenia (selected from an outpatient population, 2 females, 12 males, mean age 35.1 years) and 29 healthy subjects (8 females, 21 males, mean age 29.3 years) were scanned while they performed an auditory oddball task in which the oddball stimuli were either speech sounds or complex nonspeech sounds. Compared to controls, individuals with schizophrenia showed greater differential activation between speech and nonspeech in right temporal cortex, left superior frontal cortex, and the left temporal-parietal junction. The magnitude of the difference in the left temporal parietal junction was significantly correlated with severity of disorganized thinking. This study supports the hypothesis that aberrant functional lateralization of speech processing is an underlying feature of schizophrenia and suggests the magnitude of the disturbance in speech-processing circuits may be associated with severity of disorganized thinking.

Reduced event‐related low frequency EEG activity in schizophrenia during an auditory oddball task

This study examines EEG low frequency characteristics which have been linked to specific cognitive functions such as stimulus encoding and attention during an auditory oddball task in schizophrenia patients and healthy controls. EEG data was recorded from 17 young schizophrenia patients in a stable phase of their illness and 17 healthy controls performing an auditory oddball task. Evoked and induced delta and theta activity, N100, P300 amplitude were computed. Between 200-500 ms after a stimulus was presented, patients displayed significantly reduced P300, less evoked and induced delta and theta activity than controls. We conclude that the well known finding of P300 reduction in schizophrenia can be linked to reductions in delta and theta activity, which are a manifestation of impaired stimulus evaluation, memory retrieval, and a lack of sustained attention.

Error processing-associated event-related potentials in schizophrenia and unaffected siblings.

A reduction in the error-related negativity (ERN), a response-locked event-related potential (ERP) observed when participants commit errors during processing of stimuli, is a well-replicated cerebral abnormality in schizophrenia. However, the extent to which this abnormality reflects susceptibility to schizophrenia rather than overt change in behavioural state is unclear. As the unaffected siblings of individuals with schizophrenia are at an increased genetic risk, this study examines whether they display abnormality of the ERN similar to that observed in individuals with schizophrenia. ERPs were recorded from 29 individuals with schizophrenia, 36 unaffected siblings and 35 healthy control participants while they performed a simple Go/No-Go task. Group differences in the ERN and also in the error positivity (Pe), a response-locked positive component that follows the ERN, were investigated. Reductions of ERN amplitudes were found in both individuals with schizophrenia and siblings. No significant abnormalities were observed in Pe. The finding of reduced ERN amplitudes in siblings without prodromal symptoms supports the hypothesis that the abnormality is not a consequence of behavioural disturbance, and that it is a trait marker for susceptibility to schizophrenia, rather than being a result of illness or medication.

Time and frequency domain event-related electrical activity associated with response control in schizophrenia.

OBJECTIVE To confirm previously reported abnormalities in time domain EEG components during a go/no-go task in schizophrenia, and to test the hypothesis that patients exhibit abnormalities in frequency domain components reflecting indices of behavioural impairment. METHODS EEG data were recorded from 17 male schizophrenia patients in a stable phase of illness and 17 healthy controls. RESULTS As compared with controls, patients displayed smaller N200 amplitudes and less evoked theta for correct hit trials; and smaller N200 and P300 amplitudes and less evoked delta and theta for correct reject trials. Effect sizes were largest for evoked delta. Source localisation revealed reduced activation in schizophrenia patients during the N200 and P300 time windows in anterior and posterior cingulate, medial frontal gyrus and precuneus. Evoked delta and theta oscillations were significantly correlated with the variability of reaction times and the performance level statistic d-prime. CONCLUSIONS The results demonstrate impairment of frontal and parietal brain areas involved in response control in schizophrenia. They also suggest that the timing of oscillations in patients is less precise leading to smaller evoked amplitudes and more variable reaction times. SIGNIFICANCE These findings add to the evidence that abnormal EEG oscillations contribute to impaired behavioural control in schizophrenia.