Tilmann A. Klein

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.

Dopamine DRD2 Polymorphism Alters Reversal Learning and Associated Neural Activity

In humans, presence of an A1 allele of the DRD2/ANKK1-TaqIa polymorphism is associated with reduced expression of dopamine (DA) D2 receptors in the striatum. Recently, it was observed that carriers of the A1 allele (A1+ subjects) showed impaired learning from negative feedback in a reinforcement learning task. Here, using functional MRI (fMRI), we investigated carriers and noncarriers of the A1 allele while they performed a probabilistic reversal learning task. A1+ subjects showed subtle deficits in reversal learning. In particular, these deficits consisted of an impairment in sustaining the newly rewarded response after a reversal and in a generally decreased tendency to stick with a rewarded response. Both genetic groups showed increased fMRI signal in response to negative feedback in the rostral cingulate zone (RCZ) and anterior insula. Negative feedback that incurred a change in behavior additionally engaged the ventral striatum and a region of the midbrain consistent with the location of dopaminergic cell groups. The response of the RCZ to negative feedback increased as a function of preceding negative feedback. However, this graded response was not observed in the A1+ group. Furthermore, the A1+ group also showed diminished recruitment of the right ventral striatum and the right lateral orbitofrontal cortex (lOFC) during reversals. Together, these results suggest that a genetically driven reduction in DA D2 receptors leads to deficient feedback integration in RCZ. This, in turn, was accompanied by impaired recruitment of the ventral striatum and the right lOFC during reversals, which might explain the behavioral differences between the genetic groups.

Error awareness and the insula: Links to neurological and psychiatric diseases

Becoming aware of errors that one has committed might be crucial for strategic behavioral and neuronal adjustments to avoid similar errors in the future. This review addresses conscious error perception (“error awareness”) in healthy subjects as well as the relationship between error awareness and neurological and psychiatric diseases. We first discuss the main findings on error awareness in healthy subjects. A brain region, that appears consistently involved in error awareness processes, is the insula, which also provides a link to the clinical conditions reviewed here. Then we focus on a neurological condition whose core element is an impaired awareness for neurological consequences of a disease: anosognosia for hemiplegia (AHP). The insular cortex has been implicated in both error awareness and AHP, with anterior insular regions being involved in conscious error processing and more posterior areas being related to AHP. In addition to cytoarchitectonic and connectivity data, this reflects a functional and structural gradient within the insula from anterior to posterior. Furthermore, studies dealing with error awareness and lack of insight in a number of psychiatric diseases are reported. Especially in schizophrenia, attention-deficit hyperactivity disorder, (ADHD) and autism spectrum disorders (ASD) the performance monitoring system seems impaired, thus conscious error perception might be altered.

Adaptive coding of action values in the human rostral cingulate zone

Correctly selecting appropriate actions in an uncertain environment requires gathering experience about the available actions by sampling them over several trials. Recent findings suggest that the human rostral cingulate zone (RCZ) is important for the integration of extended action–outcome associations across multiple trials and in coding the subjective value of each action. During functional magnetic resonance imaging, healthy volunteers performed two versions of a probabilistic reversal learning task with high (HP) or low (LP) reward probabilities that required them to integrate action–outcome relations over lower or higher numbers of trials, respectively. In the HP session, subjects needed fewer trials to adjust their behavior in response to a reversal of response–reward contingencies. Similarly, the learning rate derived from a reinforcement learning model was higher in the HP condition. This was accompanied by a stronger response of the RCZ to negative feedback upon reversals in the HP condition. Furthermore, RCZ activity related to negative reward prediction errors varied as a function of the learning rate, which determines to what extent the prediction error is used to update action values. These data show that RCZ responses vary as a function of the information content provided by the environment. The more likely a negative event indicates the need for behavioral adaptations, the more prominent is the response of the RCZ. Thus, both the window of trials over which reinforcement information is integrated and adjustment of action values in the RCZ covary with the stochastics of the environment.

Continuous theta-burst stimulation (cTBS) over the lateral prefrontal cortex alters reinforcement learning bias

The prefrontal cortex is known to play a key role in higher-order cognitive functions. Recently, we showed that this brain region is active in reinforcement learning, during which subjects constantly have to integrate trial outcomes in order to optimize performance. To further elucidate the role of the dorsolateral prefrontal cortex (DLPFC) in reinforcement learning, we applied continuous theta-burst stimulation (cTBS) either to the left or right DLPFC, or to the vertex as a control region, respectively, prior to the performance of a probabilistic learning task in an fMRI environment. While there was no influence of cTBS on learning performance per se, we observed a stimulation-dependent modulation of reward vs. punishment sensitivity: Left-hemispherical DLPFC stimulation led to a more reward-guided performance, while right-hemispherical cTBS induced a more avoidance-guided behavior. FMRI results showed enhanced prediction error coding in the ventral striatum in subjects stimulated over the left as compared to the right DLPFC. Both behavioral and imaging results are in line with recent findings that left, but not right-hemispherical stimulation can trigger a release of dopamine in the ventral striatum, which has been suggested to increase the relative impact of rewards rather than punishment on behavior.

Differential Modulation of Reinforcement Learning by D2 Dopamine and NMDA Glutamate Receptor Antagonism

The firing pattern of midbrain dopamine (DA) neurons is well known to reflect reward prediction errors (PEs), the difference between obtained and expected rewards. The PE is thought to be a crucial signal for instrumental learning, and interference with DA transmission impairs learning. Phasic increases of DA neuron firing during positive PEs are driven by activation of NMDA receptors, whereas phasic suppression of firing during negative PEs is likely mediated by inputs from the lateral habenula. We aimed to determine the contribution of DA D2-class and NMDA receptors to appetitively and aversively motivated reinforcement learning. Healthy human volunteers were scanned with functional magnetic resonance imaging while they performed an instrumental learning task under the influence of either the DA D2 receptor antagonist amisulpride (400 mg), the NMDA receptor antagonist memantine (20 mg), or placebo. Participants quickly learned to select (“approach”) rewarding and to reject (“avoid”) punishing options. Amisulpride impaired both approach and avoidance learning, while memantine mildly attenuated approach learning but had no effect on avoidance learning. These behavioral effects of the antagonists were paralleled by their modulation of striatal PEs. Amisulpride reduced both appetitive and aversive PEs, while memantine diminished appetitive, but not aversive PEs. These data suggest that striatal D2-class receptors contribute to both approach and avoidance learning by detecting both the phasic DA increases and decreases during appetitive and aversive PEs. NMDA receptors on the contrary appear to be required only for approach learning because phasic DA increases during positive PEs are NMDA dependent, whereas phasic decreases during negative PEs are not.

Gender Influences on Brain Responses to Errors and Post-Error Adjustments

Sexual dimorphisms have been observed in many species, including humans, and extend to the prevalence and presentation of important mental disorders associated with performance monitoring malfunctions. However, precisely which underlying differences between genders contribute to the alterations observed in psychiatric diseases is unknown. Here, we compare behavioural and neural correlates of cognitive control functions in 438 female and 436 male participants performing a flanker task while EEG was recorded. We found that males showed stronger performance-monitoring-related EEG amplitude modulations which were employed to predict subjects’ genders with ~72% accuracy. Females showed more post-error slowing, but both samples did not differ in regard to response-conflict processing and coupling between the error-related negativity (ERN) and consecutive behavioural slowing. Furthermore, we found that the ERN predicted consecutive behavioural slowing within subjects, whereas its overall amplitude did not correlate with post-error slowing across participants. These findings elucidate specific gender differences in essential neurocognitive functions with implications for clinical studies. They highlight that within- and between-subject associations for brain potentials cannot be interpreted in the same way. Specifically, despite higher general amplitudes in males, it appears that the dynamics of coupling between ERN and post-error slowing between men and women is comparable.

Comparing the error-related negativity across groups: The impact of error- and trial-number differences

The error-related negativity (ERN or Ne) is increasingly being investigated as a marker discriminating interindividual factors and moves toward a surrogate marker for disorders or interventions. Although reproducibility and validity of neuroscientific and psychological research has been criticized, clear data on how different quantification methods of the ERN and their relation to available trial numbers affect within- and across-participant studies is sparse. Within a large sample of 863 healthy human participants, we demonstrate that, across participants, the number of errors correlates with the amplitude of the ERN independently of the number of errors included in ERN quantification per participant, constituting a possible confound when such variance is unaccounted for. Additionally, we find that ERN amplitudes reach high consistency within participants at lower trial numbers, yet when comparisons between groups of participants are desired, increasing error-trial numbers lead to higher statistical power. We derive concrete suggestions for specific types of analyses, which may help researchers to more effectively design studies and analyze error-related EEG data with the most appropriate measurement technique for the question at hand and trial number available.

Neural synchrony indexes impaired motor slowing after errors and novelty following white matter damage.

In humans, action errors and perceptual novelty elicit activity in a shared frontostriatal brain network, allowing them to adapt their ongoing behavior to such unexpected action outcomes. Healthy and pathologic aging reduces the integrity of white matter pathways that connect individual hubs of such networks and can impair the associated cognitive functions. Here, we investigated whether structural disconnection within this network because of small-vessel disease impairs the neural processes that subserve motor slowing after errors and novelty (post-error slowing, PES; post-novel slowing, PNS). Participants with intact frontostriatal circuitry showed increased right-lateralized beta-band (12-24 Hz) synchrony between frontocentral and frontolateral electrode sites in the electroencephalogram after errors and novelty, indexing increased neural communication. Importantly, this synchrony correlated with PES and PNS across participants. Furthermore, such synchrony was reduced in participants with frontostriatal white matter damage, in line with reduced PES and PNS. The results demonstrate that behavioral change after errors and novelty result from coordinated neural activity across a frontostriatal brain network and that such cognitive control is impaired by reduced white matter integrity.

Assessing error awareness without relying on introspective judgment

Becoming aware of ones own mistake may be a prerequisite for remedial and compensatory actions. Improving error awareness is of great interest for situations of human life in which either a high accuracy is emphasized or in which people have to communicate errors among each other in order to improve group performance. Having a closer understanding of what makes a person aware of an error and which brain correlates are involved in this process might open new perspectives for enhancing error awareness in multiple fields of everyday life.