Norbert Kathmann

Neural correlates of error awareness

Error processing results in a number of consequences on multiple levels. The posterior frontomedian cortex (pFMC) is involved in performance monitoring and signalling the need for adjustments, which can be observed as post-error speed-accuracy shifts at the behavioural level. Furthermore autonomic reactions to an error have been reported. The role of conscious error awareness for this processing cascade has received little attention of researchers so far. We examined the neural correlates of conscious error perception in a functional magnetic resonance imaging (fMRI) study. An antisaccade task known to yield sufficient numbers of aware and unaware errors was used. Results from a metaanalysis were used to guide a region of interest (ROI) analysis of the fMRI data. Consistent with previous reports, error-related activity in the rostral cingulate zone (RCZ), the pre-supplementary motor area (pre-SMA) and the insular cortex bilaterally was found. Whereas the RCZ activity did not differentiate between aware and unaware errors, activity in the left anterior inferior insular cortex was stronger for aware as compared to unaware errors. This could be due to increased awareness of the autonomic reaction to an error, or the increased autonomic reaction itself. Furthermore, post-error adjustments were only observed after aware errors and a correlation between post-error slowing and the hemodynamic activity in the RCZ was revealed. The data suggest that the RCZ activity alone is insufficient to drive error awareness. Its signal appears to be useful for post-error speed-accuracy adjustments only when the error is consciously perceived.

Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS

In previous studies, fast repetitive transcranial magnetic stimulation (rTMS) with a frequency > 1 Hz demonstrated substantial antidepressant effects compared to sham rTMS. However, it is not clear whether fast rTMS is superior to slow rTMS (frequency < or = 1 Hz) which is safe at therapeutically promising higher intensities. The aim of this double-blind study was to compare the action of fast, slow and sham rTMS. Eighteen patients with pharmacotherapy-resistant major depression were randomized to receive fast (10 Hz), slow (0.3 Hz) or sham rTMS with 250 stimuli/day for 5 successive days. rTMS was applied at 90% motor threshold intensity to the left dorsolateral prefrontal cortex. Scores on the Hamilton Depression Rating Scale (HDRS), but not on the Montgomery-Asberg Depression Rating Scale (MADRS), showed a statistically significant time x group interaction with a reduction of 19% after slow rTMS. However, the effect was clinically marginal and not reflected by self-rating scores. Verbal memory and reaction performance were not impaired after rTMS, and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS. In conclusion, this study further supported the safety of rTMS but does not show any clinically meaningful antidepressant efficacy of rTMS at 250 daily stimuli over 5 days in pharmacotherapy-refractory major depression.

ERP correlates of conscious error recognition: aware and unaware errors in an antisaccade task

Event‐related potential (ERP) studies identified the error‐related negativity (Ne/ERN) and the error positivity (Pe) to be associated with performance errors. However, the functional significance of these components is not yet resolved. With the present study we intended to further investigate to what extent these components are related to error awareness. ERPs were recorded during an antisaccade task, and error awareness was obtained from accuracy ratings on each trial. In accordance with earlier findings, aware and unaware errors did not differ in Ne/ERN amplitude. Whereas the late Pe (400–600 ms) shows an increased parietal positivity for aware compared with unaware errors, the early Pe (200–300 ms) shows no dissociation between aware and unaware errors. These data lend further support to the view that the Ne/ERN and the (late) Pe reflect different processes in performance monitoring. In fact the present results provide a clear replication of [ S. Nieuwenhuis et al. (2001 ) Psychophysiology, 38, 752–760], showing that the Pe is associated with error awareness and remedial action. Furthermore, it has been shown that this is only true for the late Pe, whereas the early Pe like the Ne/ERN is not modulated by error awareness.

Overactive performance monitoring in obsessive-compulsive disorder: ERP evidence from correct and erroneous reactions.

Obsessive-compulsive disorder (OCD) has repeatedly been associated with hyperactivity in fronto-striatal brain regions and regions related to performance monitoring. The aim of the current study was to further investigate electrophysiological correlates of performance monitoring. Specifically, we intended to replicate previous results revealing enhanced error-related negativity (ERN) amplitudes in OCD patients. Furthermore, we examined whether OCD patients also showed alterations regarding the correct-related negativity (CRN), the error positivity (Pe) and behavioural correlates of performance monitoring. Event-related brain potentials (ERPs) were recorded from a group of 20 OCD patients and 20 healthy control participants during a modified flanker task. Force sensitive response buttons were utilized to separate correct trials from incorrect trials with full and partial response activation. Both groups displayed substantial ERN and Pe amplitudes for full and partial errors. On error trials OCD patients showed enhanced ERN amplitudes, but group differences were not significant for the Pe and for behavioural adjustment. Further, the OCD group also exhibited enhanced CRN amplitudes and a correlation of frontal CRN amplitudes with symptom severity. These data provide further support for the view that performance monitoring is overactive in OCD. Further, since the amplitude enhancement is not specific to error processing, but is also observed for correct reactions, a response monitoring or evaluation process that contributes to both ERP components might be overactive in OCD. This is in line with fMRI results that revealed higher error- and conflict-related activity in the medial frontal cortex in OCD patients.

Prevalence of alcohol and drug abuse in schizophrenic inpatients

SummaryAll schizophrenic patients admitted consecutively either to the Psychiatric Hospital of the University of Munich (group 1,N=183) or the Mental State Hospital Haar/Munich (group 2,N=447) between 1.8.1989 and 1.2.1990 were examined to assess prevalence estimates for substance abuse in schizophrenic inpatients. psychiatric diagnosis were made according to ICD-9 criteria. Psychopathology and psychosocial variables were documented by means of the AMDP-protocol on admission and discharge. The diagnostic procedure included a detailed semi-structured interview concerning the individual alcohol and drug history and sociodemographic data, the Munich Alcoholism Screening Test (MALT), a physical examination and the screening of various laboratory parameters such as GGT and MCV, among others.The results show that substance abuse is a very common problem in schizophrenics. Lifetime prevalence rates for substance abuse were estimated at 21.8% in group 1 and 42.9% in group 2,3-month prevalence rates for substance abuse were estimated at 21.3% resp. 29.0%. Alcohol abuse was by far the most common type of abuse with prevalence estimates being 17.4% resp. 34.6%. Prevalence rates for substance abuse were much higher in the more “chronic” sample of the Mental State Hospital and in male patients. With respect to schizophrenic subtype few differences could be demonstrated with drug dependence being more common in patients with paranoid schizophrenia. The MALT proved to be a valuable sceening instrument for alcohol abuse in schizophrenics with both a high specifity and sensitivity. “Dual diagnosis” schizophrenics had a significantly higher rate of suicide attempts and were less likely to be married. Possible clinical implications of these findings are discussed.

Overactive Error-Related Brain Activity as a Candidate Endophenotype for Obsessive-Compulsive Disorder: Evidence From Unaffected First-Degree Relatives

OBJECTIVE Hyperactivity in frontal-striatal circuits is assumed to be involved in the pathophysiology of obsessive-compulsive disorder (OCD). In line with that, electrocortical correlates of overactive performance monitoring have been found to be associated with OCD independent from symptom state. The purpose of the present study was to elucidate whether overactive performance monitoring may represent a candidate endophenotype for OCD. In this case, unaffected first-degree relatives of OCD patients should also show this trait. METHOD Amplitudes of the error-related negativity and the correct-related negativity in the event-related brain potential during a flanker task were used to assess performance monitoring in three carefully matched groups: 30 patients with OCD, 30 unaffected first-degree relatives of OCD patients, and 30 healthy comparison subjects. RESULTS Relative to the healthy comparison subjects, both unaffected first-degree relatives and OCD patients showed increased error-related brain potentials. No significant correlation was obtained between amplitudes and symptom severity measures, neither in patients nor in first-degree relatives. CONCLUSIONS Increased error-related brain potentials were observed not only in OCD patients but also in unaffected first-degree relatives. Overactive error monitoring may reflect a trait marker for OCD that is independent of the presence of clinical symptoms. Thus, enhanced error-related brain activity represents a candidate neurocognitive endophenotype for OCD.

Abnormally high degree connectivity of the orbitofrontal cortex in obsessive-compulsive disorder.

IMPORTANCE Neurobiological models of obsessive-compulsive disorder (OCD) predict hyperactivity in brain circuits involving the orbitofrontal cortex and the basal ganglia, but it is unclear whether these areas are also characterized by altered brain network properties. OBJECTIVES To determine regions of abnormal degree connectivity in patients with OCD and to investigate whether connectivity measures are affected by antidepressant medication in OCD. DESIGN Case-control cross-sectional study using resting-state functional magnetic resonance imaging and a data-driven, model-free method to test for alterations in the degree of whole-brain, distant, and local connectivity in unmedicated patients with OCD compared with healthy controls. SETTING Outpatient clinic for OCD. PARTICIPANTS Twenty-three patients with OCD (12 women, 11 men) receiving no medication, 23 patients with OCD (14 women, 9 men) treated with antidepressant medication, and 2 equally sized control samples matched for age, sex, handedness, educational level, and IQ. MAIN OUTCOME MEASURES Statistical parametric maps testing the degree of distant and local functional connectivity of each voxel (hub analysis at voxel level) and OCD symptom severity. RESULTS Unmedicated patients with OCD showed greater distant connectivity in the orbitofrontal cortex and subthalamic nucleus and greater local connectivity in the orbitofrontal cortex and the putamen. Furthermore, distant connectivity of the orbitofrontal cortex and the putamen positively correlated with global OCD symptom severity. Medicated patients with OCD showed reduced local connectivity of the ventral striatum compared with the unmedicated patients. CONCLUSIONS AND RELEVANCE Consistent with neurobiological models of OCD, the orbitofrontal cortex and the basal ganglia are hyperconnected in unmedicated patients. The finding of distant connectivity alterations of the orbitofrontal cortex and the basal ganglia represents initial evidence of greater connections with distant cortical areas outside of corticostriatal circuitry. Furthermore, these data suggest that antidepressant medication may reduce connectivity within corticobasal ganglia-thalamo-cortical circuits in OCD.

Sensory gating in normals and schizophrenics: A failure to find strong P50 suppression in normals.

In a series of investigations, suppression of the auditory-evoked P50 potential to the second of two paired clicks presented 500 msec apart has been shown to be absent in schizophrenic patients, whereas normals suppress their second response to less than 20% of the first response. The phenomenon has been discussed as a possible trait marker for schizophrenia. The present study with 19 schizophrenics and 23 healthy control subjects was intended as an extended replication of the phenomenon using different stimulus parameters and a slightly different method of measuring P50 amplitudes. Replication was unsuccessful, revealing only weak suppression scores in normal subjects not significantly superior to schizophrenics. Retest sessions yielded generally stronger P50 suppression suggesting that the stability of the measure over time is questionable. The methodological changes are discussed as possible sources of this failure to replicate. It is concluded that the conditions under which P50-suppression occurs should be better clarified in order to facilitate replication.

Performance monitoring and error significance in patients with obsessive-compulsive disorder

Performance monitoring has been consistently found to be overactive in obsessive-compulsive disorder (OCD). The present study examines whether performance monitoring in OCD is adjusted with error significance. Therefore, errors in a flanker task were followed by neutral (standard condition) or punishment feedbacks (punishment condition). In the standard condition patients had significantly larger error-related negativity (ERN) and correct-related negativity (CRN) ampliudes than controls. But, in the punishment condition groups did not differ in ERN and CRN amplitudes. While healthy controls showed an amplitude enhancement between standard and punishment condition, OCD patients showed no variation. In contrast, group differences were not found for the error positivity (Pe): both groups had larger Pe amplitudes in the punishment condition. Results confirm earlier findings of overactive error monitoring in OCD. The absence of a variation with error significance might indicate that OCD patients are unable to down-regulate their monitoring activity according to external requirements.

Error Awareness in a Saccade Countermanding Task

Abstract: Stop-signal tasks can be used to analyze mechanisms of action control and error monitoring. Previous event-related potential (ERP) studies indicated enhanced stop-signal N2 amplitudes for...