Impact of emotional valence on mismatch negativity in the course of cortical face processing.

Various aspects of cortical face processing have been studied by assessing event related potentials (ERP). It has been described in the literature that mismatch negativity (MMN), a well-studied ERP, is not only modulated by sensory features but also emotional valence. However, the exact impact of emotion on the temporo-spatial profile of visual MMN during face processing remains inconsistent. By employing a sequential oddball paradigm using both neutral and emotional deviants, we were able to differentiate two distinct vMMN subcomponents. While an early subcomponent at 150-250 ms is elicited by emotional salient facial stimuli, the later subcomponent at 250-400 ms seems to reflect the detection of regularity violations in facial recognition per se, unaffected by emotional salience. Our results suggest that emotional valence is encoded in vMMN signal strength at an early stage of facial processing. Furthermore, we assume that of facial processing consists of temporo-spatially distinct, partially overlapping levels concerning different facial aspects.

Motor cognition in schizophrenia: Control of automatic imitation and mapping of action context are reduced.

The ability to imitate is considered impaired in schizophrenia patients. This assumption, however, is based on heterogeneous studies mostly targeting voluntary imitation, e.g., pantomime. Studies on automatic imitation, however, and on underlying mechanisms of top-down inhibition of automatic imitation and contextual modulation in schizophrenia are highly limited. We employed two sensorimotor paradigms to examine imitation-inhibition and action context mapping in 37 schizophrenia patients and 36 matched controls. In the first experiment, participants performed finger lifts while observing a hand executing compatible or incompatible finger lifts from the third-person perspective. The compatibility or incompatibility of these finger lifts affected participants' reaction times (RTs). The comparison of between-condition RT differences shows a larger movement compatibility effect in schizophrenia than in controls. The second experiment involved finger lifts while watching a still hand, from the first-person perspective, with constrained fingers that either corresponded or did not correspond to the participants' response fingers. Here, schizophrenia patients showed a diminished RT slowing in corresponding constraint trials. While the former results provide evidence for an impaired control of imitation in patients with schizophrenia, the latter results indicate a reduced encoding of action context. In conclusion, this study provides the first evidence for deficits of top-down control of imitation and motor context processing in the same sample of schizophrenia patients.

Mapping adaptation, deviance detection, and prediction error in auditory processing.

Various studies have suggested that auditory deviance detection is organized in a hierarchical manner with ascending levels of complexity. Event-related potentials (ERP) are considered to reflect different cortical processing stages. In the current electroencephalographic study, we employed an auditory sequence oddball paradigm to investigate different levels of cortical auditory processing and the contribution of neuronal habituation and prediction error mechanism to N1 and Mismatch Negativity (MMN). Our findings suggest that N1 reflects a lower cortical process primarily involved in the encoding of simple physical features and is thus mainly modulated by neuronal attenuation and not complex top-down mechanisms. By analyzing within-sequence signal differences, we divided the MMN into distinct subcomponents reflecting different hierachical levels of auditory processing. We determined a "first-order" MMN that reflects the processing of simple deviant features (such as frequency) and "higher-order" MMNs that occur at regularity violation of complex patterns or unexpected inputs that do not allow further predictions. In our source localization analysis, both the primary auditory cortex and left IFG were primarily involved in the detection of simple, physically deviant features, while the right IFG was associated with the processing of novel, unexpected auditory inputs and the ACC with regularity violation of known patterns. Summarizing, our results might contribute to a better understanding of the different complexities of neuronal habituation and prediction error mechanisms at different levels of cortical auditory processing.

Disentangling the interaction of sex differences and hemispheric specialization for face processing - Evidence from ERPs.

Recent studies on face processing and its hemispheric lateralization suggest that inconsistencies in earlier findings might be partially explained by sex differences, as findings from event-related potential studies indicated a more asymmetric functioning of the visual cortex during face encoding in men, whereas women seemed to display a more bilateral activation pattern. The aim of this study was to further investigate the role of sex differences in hemispheric specialization during face recognition. Fifty-four healthy participants (27 females and 27 males) engaged in a familiarity decision task in which famous and unfamiliar faces were presented in a lateralized tachistoscopic fashion with unilateral und bilateral presentation modes and measurement of event-related potentials and behavioral responses. Results showed a clear N170 component for males and females in all experimental conditions. No hemispheric differences of the N170 were observed in the bilateral condition and both groups showed larger right-hemispheric than left-hemispheric N170 amplitudes in the left visual field condition. In the right visual field condition, however, only female participants showed significantly larger left-hemispheric compared to right-hemispheric N170 amplitudes, whereas male participants did not show such a modulation. The effect corresponds to a greater responsivity of left-hemispheric processes underlying the N170 component in female participants. Further analyses revealed N170 differences in the left and right hemisphere for females only, when stimuli were presented unilaterally. In contrast, this modulation of N170 amplitudes was only observed in the left hemisphere in males. The results suggest a stronger hemispheric lateralization in men than in women during face processing.

Emotional context restores cortical prediction error responses in schizophrenia.

The mismatch negativity (MMN) deficit in schizophrenia is a consistently replicated finding and is considered a potential biomarker. From the cognitive neuroscience perspective, MMN represents a cortical correlate of the prediction error, a fundamental computational operator that may be at the core of various cognitive and clinical deficits observed in schizophrenia. The impact of emotion on cognitive processes in schizophrenia is insufficiently understood, and its impact on basic operators of cortical computation is largely unknown. In the visual domain, the facial expression mismatch negativity (EMMN) offers an opportunity to investigate basic computational operators in purely cognitive and in emotional contexts. In this study, we asked whether emotional context enhances cortical prediction error responses in patients with schizophrenia, as is the case in normal subjects. Therefore, seventeen patients with schizophrenia and eighteen controls completed a visual sequence oddball task, which allows for directly comparing MMN components evoked by deviants with high, intermediate and low emotional engagement. Interestingly, patients with schizophrenia showed pronounced deficits in response to neutral stimuli, but almost normal responses to emotional stimuli. The dissociation between impaired MMN and normal EMMN suggests that emotional context not only enhances, but restores cortical prediction error responses in patients with schizophrenia to near-normal levels. Our results show that emotional processing in schizophrenia is not necessarily defect; more likely, emotional processing heterogeneously impacts on cognition in schizophrenia. In fact, this study suggests that emotional context may even compensate for cognitive deficits in schizophrenia that are, in a different sensory domain, discussed as biomarkers.

Face identity is encoded in the duration of N170 adaptation.

Previous studies assessing the involvement of the face-sensitive N170 component of the event-related potential (ERP) in the processing of face identity have shown controversial results when assessing N170 amplitude in repetition suppression (RS) designs. On the other hand, N170 adaptation is robustly associated with the inter-stimulus interval (ISI) between immediate face repetitions. Interestingly, interactions of face identity and ISI could provide valuable information on early encoding of face identity, but have not been investigated so far. We employed a repetition suppression paradigm using identical and non-identical repetitions as well as parametrically varied ISIs between 500 msec and 2,000 msec in 27 healthy subjects to investigate N170 adaptation effects. Both face identity and varying ISIs significantly influenced N170 adaptation effects, albeit with small effects sizes. Most importantly, however, face identity and ISIs strongly interacted with rapid N170 amplitude recovery in non-identical trials, but sustained N170 adaptation in identical trials. We excluded low-level sensory contributions to the N170 adaptation effect by analyzing the P1 component and by running an additional experiment employing different stimulus sizes. This specific result strongly argues in favor of neuronal sensitivity to face identity, which is primarily mirrored in the N170 temporal decay function that essentially differentiates identical and non-identical face trials. In general, taking advantage of the temporal dimension of adaptation processes, i.e., their decay over time, provides additional dissections of neuronal function into feature-specific selectivity versus non-selectivity.

Single-subject prediction of response inhibition behavior by event-related potentials.

Much research has been devoted to investigating response inhibition and the neuronal processes constituting this essential cognitive faculty. However, the nexus between cognitive subprocesses, behavior, and electrophysiological processes remains associative in nature. We therefore investigated whether neurophysiological correlates of inhibition subprocesses merely correlate with behavioral performance or actually provide information expedient to the prediction of behavior on a single-subject level. Tackling this question, we used different data-driven classification approaches in a sample of n = 262 healthy young subjects who completed a standard Go/Nogo task while an EEG was recorded. On the basis of median-split response inhibition performance, subjects were classified as "accurate/slow" and "less accurate/fast." Even though these behavioral group differences were associated with significant amplitude variations in classical electrophysiological correlates of response inhibition (i.e., N2 and P3), they were not predictive for group membership on a single-subject level. Instead, amplitude differences in the Go-P2 originating in the precuneus (BA7) were shown to predict group membership on a single-subject level with up to 64% accuracy. These findings strongly suggest that the behavioral outcome of response inhibition greatly depends on the amount of cognitive resources allocated to early stages of stimulus-response activation during responding. This suggests that research should focus more on early processing steps during responding when trying to understand the origin of interindividual differences in response inhibition processes.

Mirror neuron deficit in schizophrenia: Evidence from repetition suppression.

BACKGROUND: Schizophrenia is associated with impaired cognition, especially cognition in social contexts. The mirror neuron system (MNS) serves as an important neuronal basis for social cognitive skills; however, previous investigations on the integrity of MNS function in schizophrenia remain approximate. METHODS: We employed a repetition suppression paradigm that allows for measuring neuronal responses to gesture observation and gesture execution. Cross-modal repetition suppression, i.e., adaptation between observe/execute and execute/observe conditions, was defined as the decisive experimental condition characterizing the unique sensori-motor properties of mirror neurons. Event-related potentials (ERPs) were assessed in 15 schizophrenia patients and 15 matched controls. RESULTS: We isolated an ERP signature of specific adaptation effects to identical hand gestures. Of critical importance, this ERP signature indicated intact intra-modal adaptive pattern, i.e., observe/observe and execute/execute, of comparable magnitude between groups, but deficient cross-modal adaptation, i.e., observe/execute and execute/observe, in schizophrenia patients. CONCLUSION: Our data provide robust evidence that pure perception and execution of hand gestures are relatively intact in schizophrenia. In contrast, visuo-motor transformation processes mediated by the MNS seem to be specifically disturbed in schizophrenia. These results unambiguously demonstrate MNS deficits in schizophrenia and extend our understanding of the neuronal bases of social dysfunction in this disorder.

Emotional context facilitates cortical prediction error responses.

In the predictive coding framework, mismatch negativity (MMN) is regarded a correlate of the prediction error that occurs when top-down predictions conflict with bottom-up sensory inputs. Expression-related MMN is a relatively novel construct thought to reflect a prediction error specific to emotional processing, which, however, has not yet been tested directly. Our paradigm includes both neutral and emotional deviants, thereby allowing for investigating whether expression-related MMN is emotion-specific or unspecifically arises from violations of a given sequence. Twenty healthy participants completed a visual sequence oddball task where they were presented with (1) sequence deviants, (2) emotional sequence deviants, and (3) emotional deviants. Mismatch components were assessed at ventral occipitotemporal scalp sites and analyzed regarding their amplitudes, spatiotemporal profiles, and neuronal sources. Expression-related MMN could be clearly separated from its neutral counterpart in all investigated aspects. Specifically, expression-related MMN showed enhanced amplitude, shorter latency, and different neuronal sources. Our results, therefore, provide converging evidence for a quantitative specificity of expression-related MMN and seems to provide an opportunity to study prediction error during preattentive emotional processing. Our neurophysiological evidence ultimately suggests that a basic cognitive operator, the prediction error, is enhanced at the cortical level by processing of emotionally salient stimuli.

Auditory mismatch negativity and repetition suppression deficits in schizophrenia explained by irregular computation of prediction error.

BACKGROUND: The predictive coding model is rapidly gaining attention in schizophrenia research. It posits the neuronal computation of residual variance ('prediction error') between sensory information and top-down expectation through multiple hierarchical levels. Event-related potentials (ERP) reflect cortical processing stages that are increasingly interpreted in the light of the predictive coding hypothesis. Both mismatch negativity (MMN) and repetition suppression (RS) measures are considered a prediction error correlates based on error detection and error minimization, respectively. METHODS: Twenty-five schizophrenia patients and 25 healthy controls completed auditory tasks designed to elicit MMN and RS responses that were investigated using repeated measures models and strong spatio-temporal a priori hypothesis based on previous research. Separate correlations were performed for controls and schizophrenia patients, using age and clinical variables as covariates. RESULTS: MMN and RS deficits were largely replicated in our sample of schizophrenia patients. Moreover, MMN and RS measures were strongly correlated in healthy controls, while no correlation was found in schizophrenia patients. Single-trial analyses indicated significantly lower signal-to-noise ratio during prediction error computation in schizophrenia. CONCLUSIONS: This study provides evidence that auditory ERP components relevant for schizophrenia research can be reconciled in the light of the predictive coding framework. The lack of any correlation between the investigated measures in schizophrenia patients suggests a disruption of predictive coding mechanisms in general. More specifically, these results suggest that schizophrenia is associated with an irregular computation of residual variance between sensory input and top-down models, i.e. prediction error.

[Mental Health Care Utilization of First Generation Vietnamese Migrants in Germany]. / Inanspruchnahme ambulanter psychiatrischer Versorgung bei vietnamesischen Migranten der ersten Generation in Deutschland.

OBJECTIVE: Vietnamese migrants underutilize and are a "hard to reach group" within the existing mental health care system in Germany. METHODS: We analyzed migration related and clinical data for all first-time Vietnamese migrants seeking psychiatric help, within the first 30 months of a newly established outpatient clinic, offering culture-sensitive psychiatric treatment in native Vietnamese language. RESULTS: Most first time patients were female, first generation Vietnamese migrants with poor German language skills. Only 1 /3 of all patients had a psychiatric history, while this number was higher in patients with schizophrenia. Over time, more first time patients with depression were seeking psychiatric care, accompanied with an increase of non-professional referrals within the Vietnamese communities. CONCLUSION: This first study on mental health care utilization in Vietnamese migrants in Germany points towards the fact that "migrants" cannot be considered as a homogeneous group. Mental health care utilization must be evaluated for specific migrant groups, and can be initially improved if offered in native language and when it is referred to by members of migrant communities.

ERP adaptation provides direct evidence for early mirror neuron activation in the inferior parietal lobule.

Mirror neuron systems are frequently investigated by assessing overlapping brain activity during observation and execution of actions; however, distinct neuronal subpopulations may be activated that fall below the spatial resolution of magnetic resonance techniques. This shortfall can be resolved using repetition suppression paradigms that identify physiological adaptation processes caused by repeated activation of identical neuronal circuits. Here, event-related potentials were used to investigate the time course of mirror neuron circuit activation using repetition suppression within and across action observation and action execution modalities. In a lip-reading and speech production paradigm, the N170 component indexed stimulus repetition by adapting to both cross-modal and intra-modal repetitions in the left hemisphere. Neuronal source localization revealed activation of the left inferior parietal lobule during cross-modal relative to intra-modal trials. These results provide support for the position that the same neuronal circuits are activated in perceiving and performing articulatory actions. Moreover, our data strongly suggest that inferior parietal lobule mirror neurons are activated relatively early in time, which indicates partly automatic processes of linguistic perception and mirroring. Repetition suppression paradigms therefore help to elucidate neuronal correlates of different cognitive processes and may serve as a starting point for advanced electrophysiological research on mirror neurons.

Spatiotemporal dynamics of early cortical gesture processing.

Gesture processing has been consistently shown to be associated with activation of the inferior parietal lobe (IPL); however, little is known about the integration of IPL activation into the temporal dynamics of early sensory areas. Using a temporally graded repetition suppression paradigm, we examined the activation and time course of brain areas involved in hand gesture processing. We recorded event-related potentials in response to stimulus pairs of static hand images forming gestures of the popular rock-paper-scissors game and estimated their neuronal generators. We identified two main components associated with adaptive patterns related to stimulus repetition. The N190 component elicited at temporo-parietal sites adapted to repetitions of the same gesture and was associated with right-hemispheric extrastriate body area activation. A later component at parieto-occipital sites demonstrated temporally graded adaptation effects for all gestures with a left-hemispheric dominance. Source localization revealed concurrent activations of the right extrastriate body area, fusiform gyri bilaterally, and the left IPL at about 250 ms. The adaptation pattern derived from the graded repetition suppression paradigm demonstrates the functional sensitivity of these sources to gesture processing. Given the literature on IPL contribution to imitation, action recognition, and action execution, IPL activation at about 250 ms may represent the access into specific cognitive routes for gesture processing and may thus be involved in integrating sensory information from cortical body areas into subsequent visuo-motor transformation processes.

Smoking improves divided attention in schizophrenia.

RATIONALE: Smoking is highly prevalent in schizophrenia, and there is evidence for beneficial effects on neurocognition. Smoking is therefore hypothesized a self-medication in schizophrenia. Although much effort is devoted to characterize those cognitive domains that potentially benefit from smoking, divided attention has not yet been investigated. OBJECTIVES: The aim of this study was to analyze the interactional effects of diagnosis of schizophrenia and smoking history on divided attention. METHODS: We investigated behavioral measures of divided attention in a sample of 48 schizophrenic patients and 48 controls (24 current smokers and non-smokers each) carefully matched for age, sex, education, verbal IQ, and smoking status with general linear models. RESULTS: Most important within the scope of this study, significant interactions were found for valid reactions and errors of omission: Performance substantially increased in smoking schizophrenic patients, but not in controls. Further, these interactions were modified by sex, driven by female schizophrenic patients who showed a significant behavioral advantage of smokers over non-smokers, other than male schizophrenic patients or healthy controls who did not express this sex-specific pattern. CONCLUSIONS: Results suggest a positive effect of smoking history on divided attention in schizophrenic patients. This study provides first evidence that the complex attention domain of divided attention is improved by smoking, which further substantiates the self-medication hypothesis of smoking in schizophrenia, although this has been shown mainly for sustained and selective attention. Gender-specific effects on cognition need to be further investigated.

Assessing long-term test-retest reliability of the CPT-IP in schizophrenia.

BACKGROUND: The Continuous Performance Test-Identical Pairs version (CPT-IP) is a well-established measure of sustained attention, and its more challenging versions are particularly suited to detect subtle processing deficits in patients with schizophrenia. However, while there are few longitudinal samples for the CPT-IP, no study has addressed stability for more than two month in patients with schizophrenia. Assessing long-term test-retest reliability of the CPT-IP would facilitate the ability of clinicians to draw conclusions from studies involving interventions as long term cognitive or pharmacological treatments. The present study assessed 12 month test-retest reliability for the two most challenging versions of CPT-IP (4-digit and shapes) in a matched sample of clinically stable schizophrenia outpatients and healthy controls. METHODS: Fifty clinically stable schizophrenia outpatients and 50 healthy controls were assessed with the CPT-IP for the 4-digit and shape conditions. From these, 40 patients and 47 controls were reassessed with an average interval of 12.3 months between test sessions. Test-retest reliability was analyzed with Pearson correlations and results were compared with previous data involving healthy controls and short-term studies in patients with schizophrenia. RESULTS: Especially d' and hit rate discriminated well between patients with schizophrenia and healthy controls for both CPT-IP conditions and at both test sessions. Healthy controls demonstrated sufficient long term test-retest correlations of d', hit rate and reaction time for both the 4-digit and shape conditions. However, in schizophrenia patients, long-term reliability correlations were at best moderate for d' and hit rate only. CONCLUSIONS: The current study provides further evidence that d' and hit rate yield consistent cross-sectional discrimination sensitivity. At best moderate long-term test-retest reliability of d' in schizophrenia outpatients may be not sufficient for practical use of this measure in long term clinical trials.

Neurocognitive pattern analysis reveals classificatory hierarchy of attention deficits in schizophrenia.

Attention deficits, among other cognitive deficits, are frequently observed in schizophrenia. Although valid and reliable neurocognitive tasks have been established to assess attention deficits in schizophrenia, the hierarchical value of those tests as diagnostic discriminants on a single-subject level remains unclear. Thus, much research is devoted to attention deficits that are unlikely to be translated into clinical practice. On the other hand, a clear hierarchy of attention deficits in schizophrenia could considerably aid diagnostic decisions and may prove beneficial for longitudinal monitoring of therapeutic advances. To propose a diagnostic hierarchy of attention deficits in schizophrenia, we investigated several facets of attention in 86 schizophrenia patients and 86 healthy controls using a set of established attention tests. We applied state-of-the-art machine learning algorithms to determine attentive test variables that enable an automated differentiation between schizophrenia patients and healthy controls. After feature preranking, hypothesis building, and hypothesis validation, the polynomial support vector machine classifier achieved a classification accuracy of 90.70% ± 2.9% using psychomotor speed and 3 different attention parameters derived from sustained and divided attention tasks. Our study proposes, to the best of our knowledge, the first hierarchy of attention deficits in schizophrenia by identifying the most discriminative attention parameters among a variety of attention deficits found in schizophrenia patients. Our results offer a starting point for hierarchy building of schizophrenia-associated attention deficits and contribute to translating these concepts into diagnostic and therapeutic practice on a single-subject level.

Critical evaluation of auditory event-related potential deficits in schizophrenia: evidence from large-scale single-subject pattern classification.

Event-related potential (ERP) deficits associated with auditory oddball and click-conditioning paradigms are among the most consistent findings in schizophrenia and are discussed as potential biomarkers. However, it is unclear to what extend these ERP deficits distinguish between schizophrenia patients and healthy controls on a single-subject level, which is of high importance for potential translation to clinical routine. Here, we investigated 144 schizophrenia patients and 144 matched controls with an auditory click-conditioning/oddball paradigm. P50 and N1 gating ratios as well as target-locked N1 and P3 components were submitted to conventional general linear models and to explorative machine learning algorithms. Repeated-measures ANOVAs revealed significant between-group differences for the oddball-locked N1 and P3 components but not for any gating measure. Machine learning-assisted analysis achieved 77.7% balanced classification accuracy using a combination of target-locked N1 and P3 amplitudes as classifiers. The superiority of machine learning over repeated-measures analysis for classifying schizophrenia patients was in the range of about 10% as quantified by receiver operating characteristics. For the first time, our study provides large-scale single-subject classification data on auditory click-conditioning and oddball paradigms in schizophrenia. Although our study exemplifies how automated inference may substantially improve classification accuracy, our data also show that the investigated ERP measures show comparably poor discriminatory properties in single subjects, thus illustrating the need to establish either new analytical approaches for these paradigms or other paradigms to investigate the disorder.