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.

Changes in Electric Brain Response to Affective Stimuli in the First Week of Antidepressant Treatment: An Exploratory Study.

INTRODUCTION: Asymmetrical alpha and frontal theta activity have been discussed as neurobiological markers for antidepressant treatment response. While most studies focus on resting-state EEG, there is evidence that task-related activity assessed at multiple time points might be superior in detecting subtle early differences. METHODS: This was a naturalistic study design assessing participants in a psychiatric in- and outpatient hospital setting. We investigated stimulus-related EEG asymmetry (frontal and occipital alpha-1 and alpha-2) and power (frontal midline theta) assessed at baseline and 1 week after initiation of pharmacological depression treatment while presenting affective stimuli. We then compared week 4 responders and nonresponders to antidepressant treatment. RESULTS: Follow-up analyses of a significant group × emotion × time interaction (p < 0.04) for alpha-1 asymmetry showed that responders differed significantly at baseline in their asymmetry scores in response to sad compared to happy faces with a change in this pattern 1 week later. Nonresponders did not show this pattern. No significant results were found for alpha-2, occipital alpha-1, and occipital alpha-2 asymmetry or frontal midline theta power. DISCUSSION: Our study addresses the gap in comparisons of task-related EEG activity changes measured at two time points and supports the potential value of this approach in detecting early differences in responders versus nonresponders to pharmacological treatment. Important limitations include the small sample size and the noncontrolled study design.

Fronto-lateral alpha power asymmetry in panic disorder.

Resting state alpha power asymmetry in frontal and temporal regions has been reported in various clinical populations, possibly indicating deficits in prefrontal control. In panic disorder (PD), results regarding alpha asymmetric activity to date have been mixed. This study compared 55 PD patients and 42 healthy controls (HC) with regards to resting state alpha power asymmetry. Our results show more right-than-left fronto-lateral alpha power in PD, whereas at other sites and in HC no significant differences were detected. These results support the notion of altered neurobiological processes in PD that possibly represent a vulnerability to the experience of panic attacks. Further studies are needed to clarify potential causal implications of this finding in the genesis of PD, as well as to specify the functional significance of fronto-lateral alpha power asymmetry in PD.

EEG Frontal Asymmetry and Theta Power in Unipolar and Bipolar Depression.

BACKGROUND: Distinguishing between unipolar and bipolar depression is of high clinical relevance. However, there is sparse research directly comparing these groups in terms of EEG activity. METHOD: We investigated 87 participants' left and right EEG frontal alpha-1, alpha-2, and theta activity related to happy and sad face stimuli in unipolar (UD, n=33) and bipolar (BD, n=22) depressed participants, and controls without depression (HC, n=32). RESULTS: Post-hoc analysis of an observed hemisphere x group interaction (p< .037) showed significant differences in alpha-1 asymmetry only for the comparison of UD and HC (p< .006). Further analysis of a significant emotion x group interaction (p= .001) revealed a differential impact of stimulus valence on theta power between the groups (p< .001). The valence dependent theta power of the BD differed from that of the UD (p< .0002) and the HC (p< .004). Alpha-1 asymmetry classified HC and both depressed groups with an accuracy of .69. Valence-related theta classified BD from UD with an accuracy of .83. Leave-one-out cross validation resulted in slightly reduced accuracy. LIMITATIONS: Important limitations were the small sample size and that subjects were not medication-free. CONCLUSIONS: Our results demonstrate the value of simple, task related EEG activity for differentiating not only healthy individuals from those with depression, but also individuals with unipolar depression from those with bipolar depression.

Peripheral oxytocin is inversely correlated with cognitive, but not emotional empathy in schizophrenia.

Endogenous oxytocin has been associated with different aspects of social cognition in healthy subjects and patients with schizophrenia. In this pilot study, we investigated the relationship between plasma oxytocin and oxytocin level changes induced by empathy-eliciting, attachment-related movie scenes with correlates of cognitive and emotional empathy in patients and healthy controls. The Multifaceted Empathy Test (MET) and the Interpersonal Reactivity Index (IRI) were administered to patients with schizophrenia (N = 35, 12 females) and healthy controls (N = 35, 12 females) to estimate dimensions of cognitive and emotional empathy. Peripheral basal oxytocin concentrations and oxytocin responses to movie-based emotional stimuli were assessed using radioimmunoassay with sample extraction. In patients, induced oxytocin level changes were inversely correlated with MET cognitive empathy regarding negative emotional states. Controlling for non-social cognition and age revealed a significant negative association between basal oxytocin levels and MET cognitive empathy for positive emotions. In healthy subjects, oxytocin reactivity was inversely correlated with the IRI subscale "fantasy". Oxytocin was not related to any measure of emotional empathy. A hyper-reactive oxytocin system might be linked to impaired cognitive empathy as a part of a dysfunctional regulative circuit of attachment-related emotions and interpersonal stressors or threats by attribution of meaning. Healthy adults with a disposition to identify with fictional characters showed lower oxytocin reactivity, possibly indicating familiarity with movie-based stimuli. The oxytocinergic system may be involved in maladaptive coping mechanisms in the framework of impaired mentalizing and associated dysfunctional responses to interpersonal challenges in schizophrenia.

Test-Retest Reliability of Frontal and Parietal Alpha Asymmetry during Presentation of Emotional Face Stimuli in Healthy Subjects.

Resting-state and event-related frontal alpha asymmetry have been suggested as potential neurobiological biomarkers for depression and other psychiatric conditions. To be used as such, sufficient test-retest reliability needs to be demonstrated. However, test-retest reliability is underinvestigated for event-related alpha asymmetry. The objective of this study was to examine both short-term within-session and long-term between-session reliability of stimulus-related medial and lateral frontal as well as parietal alpha EEG asymmetry in healthy subjects during a simple emotional face processing task. Twenty-three healthy adults participated in two sessions with a test-retest interval of about 1 week. Reliability was estimated with Pearson's correlation coefficient and paired t test. Results revealed moderate to high within-session reliability of stimulus-related alpha asymmetry for all electrode sites and both conditions. Alpha asymmetry mean values did not change significantly within sessions. Between-session reliability was fair for frontomedial and moderate for frontolateral stimulus-related asymmetry. Exploratory exclusion of subjects with unstable between-session self-rating scores of emotional state and empathy toward stimuli resulted in some higher reliability values. Our results indicate that stimulus-related alpha asymmetry may serve as a useful electrophysiological tool given its adequate within-session reliability. However, long-term stability of stimulus-related frontal alpha asymmetry over 1 week was comparatively low and varied depending on electrode position. Influencing state factors during EEG recording, such as current mood or stimulus engagement, should be considered in future study designs and analyses. Further, we recommend to analyze alpha asymmetry from both frontomedial and frontolateral sites.

P50, N100, and P200 Sensory Gating in Panic Disorder.

Panic disorder (PD) has been linked to abnormalities in information processing. However, only little evidence has been published for sensory gating in PD. Sensory gating describes the brain's ability to exclude stimuli of low relevance from higher level information processing, thereby sustaining efficient cognitive processing. Deficits in sensory gating have been associated with various psychiatric conditions, most prominently schizophrenia. In this case-control event-related potential study, we tested 32 patients with PD and 39 healthy controls in a double click paradigm. Both groups were compared with regard to pre-attentive (P50), early-attentive (N100), and late-attentive (P200) sensory gating indices. Contrary to a hypothesized deficit, PD patients and healthy controls showed no differences in P50, N100 and P200 values. These results suggest that sensory gating seems to be functional across the pre-attentive, early-attentive, and late-attentive time span in this clinical population. Given this consistency across auditory sensory gating indices, further research aiming to clarify information processing deficits in PD should focus on other neurophysiological markers to investigate information processing deficits in PD (eg, P300, error-related negativity or mismatch negativity).

Reduced Sensitivity to Non-Fear-Related Stimulus Changes in Panic Disorder.

Panic disorder (PD) is associated with increased body vigilance and reduced cognitive resources directed at non-fear-related stimuli, particularly in the absence of stimulus-rich environments. To date, only few studies have investigated whether this deficit in PD is reflected in reduced mismatch negativity (MMN), an event-related potential indexing preattentive sensitivity to unexpected stimulus changes. We tested 35 patients affected by PD and 42 matched healthy controls in an oddball paradigm, using frequency and duration deviant stimuli to measure auditory MMN. PD patients displayed reduced duration MMN amplitudes in comparison to healthy controls. No group differences were detected for duration MMN latency, as well as frequency MMN indices. Results support the notion of reduced processing of non-fear-related stimuli in PD patients, particularly with regard to the preattentive processing of sound duration deviants. Additionally, our findings are in line with clinical studies reporting divergent deficits in preattentive processing of frequency and duration deviants.

Treatment response of lithium augmentation in geriatric compared to non-geriatric patients with treatment-resistant depression.

BACKGROUND: Lithium augmentation (LA) of antidepressants is an effective strategy for treatment-resistant depression (TRD). Nevertheless, it is rarely used in geriatric patients. The purpose of this study was to investigate treatment response of LA in geriatric compared to non-geriatric patients. METHOD: In a prospective multicenter cohort study, severity of depression was measured weekly in 167 patients with unipolar depression (nage≥65years = 22; nage<65years = 145) at baseline and over at least four weeks of LA. RESULTS: Geriatric patients showed a significantly better response to LA compared to non-geriatric patients (Hazard Ratio = 1.91; p = 0.04). LIMITATIONS: An important limitation of our study is the lack of a control group of LA and the missing evaluation of side effects in both groups. CONCLUSIONS: This is the first study investigating the efficacy of LA for TRD in geriatric compared to non-geriatric patients. Our data suggest that LA is an effective treatment option in geriatric patients that clinicians might consider more frequently and earlier on in the course of treatment.

[Coercive Interventions in Psychiatry: Prevention and Patients' Preferences]. / Psychiatrische Zwangsmaßnahmen: Prävention und Präferenzen aus Patientenperspektive.

Objective This study explores patients' preferences and measures of prevention of coercive methods in psychiatric treatment. Methods Structured interviews of 90 patients with psychotic disorders were undertaken, most of whom had previously experienced coercive methods. Results Participants saw preventive potential in a wider availability of individual non-pharmacological therapy, improvement of staff professional competence and communication skills, high staff-to-patient ratios and retreat facilities. The majority of participants preferred forced medication and manual restraint in case of self-endangerment, and forced medication and mechanical restraint in the event of endangerment of others. Conclusion Patients' suggestions relating to prevention of coercion are in line with most expert's opinions. In case coercive methods are required, manual restraint and application of forced medication is accepted as the treatment of choice according to most patients in case of self-endangerment.

Opposing Effects of Cannabis Use on Late Auditory Repetition Suppression in Schizophrenia Patients and Healthy Control Subjects.

BACKGROUND: Chronic cannabis use may cause neurocognitive deficits and increase the risk of psychosis. Nevertheless, the effects of cannabis use on neurocognitive functioning in schizophrenia have remained largely unspecified. METHODS: Here, we studied repetition suppression of auditory event-related responses in a paired-stimulus design in a mixed sample of schizophrenia patients (n = 34) and healthy control subjects (n = 45) with chronic heavy cannabis use and schizophrenia patients (n = 33) and healthy control subjects (n = 61) without cannabis use. RESULTS: Repeated measures analysis yielded an overall significant reduction of P50 amplitude between first and second stimulus (p < .02), which was not different between the groups, a reduction of N100 amplitude, which was different for schizophrenia patients compared with healthy control subjects independent of cannabis use (p < .02), and a significant interaction between diagnosis and chronic cannabis use on the reduction of the P200 amplitude (p < .001). While chronic cannabis use was related with increased P200 suppression ratios in control subjects (with chronic cannabis use: 0.55 ± 0.04; without chronic cannabis use: 0.40 ± 0.03; p < .02), the reverse effect was found in schizophrenia (with chronic cannabis use: 0.36 ± 0.05; without chronic cannabis use: 0.54 ± 0.05; p < .02). This result remained significant after inclusion of potential confounders. Total lifetime cannabis use showed a significant correlation with the P200 suppression ratio in otherwise healthy control subjects (r = .28, p < .007). By contrast, the duration of time since last cannabis use was significantly correlated with the P200 suppression ratio in schizophrenia patients (r = .42, p < .002). CONCLUSIONS: In aggregate, these diverging effects of chronic cannabis use on P200 repetition suppression may suggest underlying alterations in the endocannabinoid system in schizophrenia.

Attentional dysfunction in abstinent long-term cannabis users with and without schizophrenia.

Long-term cannabis use may confer cognitive deficits and increased risk of psychosis. However, the relationship between cannabis use and schizophrenia is complex. In particular, little is known about the effects of chronic cannabis use on the attention-related electric brain response in schizophrenia. We investigated auditory novelty and oddball P300 evoked potentials in a mixed sample of first-episode and chronic schizophrenic patients and healthy controls with (SZCA, n = 20; COCA, n = 20, abstinence ≥28 days) or without (SZ, n = 20; CO, n = 20) chronic cannabis use. Duration of regular cannabis use was 8.3 ± 5.6 (SZCA) and 9.1 ± 7.1 (COCA) years. In general, schizophrenic patients showed reduced P300 amplitudes. Cannabis use was associated with both a reduced early and late left-hemispheric novelty P300. There was a significant 'diagnosis × cannabis' interaction for the left-hemispheric late novelty P300 in that cannabis use was associated with a reduced amplitude in the otherwise healthy but not in the schizophrenic group compared with their relative control groups (corrected p < 0.02; p > 0.9, respectively). The left-hemispheric late novelty P300 in the otherwise healthy cannabis group correlated inversely with amount and duration of cannabis use (r = -0.50, p = 0.024; r = -0.57, p = 0.009, respectively). Our study confirms attentional deficits with chronic cannabis use. However, cannabis use may lead to different cognitive sequelae in patients with schizophrenia and in healthy controls, possibly reflecting preexisting alterations in the endocannabinoid system in schizophrenia.

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.

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.

Pretreatment anterior cingulate activity predicts antidepressant treatment response in major depressive episodes.

Major depressive disorder leads to substantial individual and socioeconomic costs. Despite the ongoing efforts to improve the treatment for this condition, a trial-and-error approach until an individually effective treatment is established still dominates clinical practice. Searching for clinically useful treatment response predictors is one of the most promising strategies to change this quandary therapeutic situation. This study evaluated the predictive value of a biological and a clinical predictor, as well as a combination of both. Pretreatment EEGs of 31 patients with a major depressive episode were analyzed with neuroelectric brain imaging technique to assess cerebral oscillations related to treatment response. Early improvement of symptoms served as a clinical predictor. Treatment response was assessed after 4 weeks of antidepressant treatment. Responders showed more slow-frequency power in the right anterior cingulate cortex compared to non-responders. Slow-frequency power in this region was found to predict response with good sensitivity (82 %) and specificity (100 %), while early improvement showed lower accuracy (73 % sensitivity and 65 % specificity). Combining both parameters did not further improve predictive accuracy. Pretreatment activity within the anterior cingulate cortex is related to antidepressive treatment response. Our results support the search for biological treatment response predictors using electric brain activity. This technique is advantageous due to its low individual and socioeconomic burden. The benefits of combining both, a clinically and a biologically based predictor, should be further evaluated using larger sample sizes.

Early orbitofrontal hyperactivation in obsessive-compulsive disorder.

Dysfunctional activity in the orbitofrontal cortex (OFC) is one of the core features in the pathophysiology of obsessive-compulsive disorder (OCD). Neuroimaging studies indicate orbitofrontal hyperactivation during the resting state as well as during symptom provocation, whereas orbitofrontal hypoactivation has been reported during tasks designed to dissociate specific cognitive processes. Combined magnetoencephalic and functional magnetic resonance imaging studies show early involvement of the OFC in stimulus processing in healthy subjects. However, it is unclear whether OFC activation is dysfunctional at an early stage in patients with OCD. We investigated early electrical OFC activation evoked by reward and punishment feedback in a visual probabilistic object reversal task (pORT). Patients with OCD (n=23) and healthy controls (n=27), matched for gender, age and educational level, performed the pORT during a 29-channel electroencephalographic recording. Low resolution brain electromagnetic tomography was applied to localize orbitofrontal sources of neuronal activity at 80 to 200 ms post-stimulus. Group comparison showed significantly higher orbitofrontal activation in OCD patients at 100-120 ms after the reward stimulus. No group differences were found with respect to OFC activation in response to punishment stimuli and in task performance. Results substantiate dysfunctional OFC activity at a very early stage in the processing of reward stimuli in patients with OCD. Our results provide support for the assumption that the OFC plays a more active role in the processing of visual stimuli as previously supposed. As orbitofrontal hyperactivation following rewarding feedback occurred as early as 100 ms after receipt of the visual stimulus in patients with OCD, and as we did not find any OFC dysfunction following negative feedback, our findings may point towards a specific early disturbance of reward processing in OCD. This finding might have implications for cognitive behavioural therapy of this disorder.

Neurophysiological effects of cannabinoids: implications for psychosis research.

It is widely accepted that there is a close relationship between cannabis use, the endocannabinoid system, and psychosis. In particular, cannabis use has the potential to trigger the onset of psychosis in vulnerable individuals and to exacerbate psychotic symptomatology in schizophrenia patients, including positive, negative, and cognitive symptoms. With regard to the cognitive dysfunctions as a core feature of schizophrenia, overlapping deficits in the domains of attention, memory, and executive functioning have been observed between chronic cannabis use and the disease. In this overview, we report on human clinical and experimental studies investigating the acute and chronic effects of cannabinoids on specific neurophysiological measures, i.e., the P50 suppression, the mismatch negativity, and the P300 potential, that consistently showed characteristic abnormalities in schizophrenia. Based on the results, we discuss some explanations on the putative mechanisms involving the endocannabinoid system and its interactions with other neuromodulators that might form the neural substrates underlying cannabis-induced cognitive impairments and help understand the neurobiology underpinning the development of cognitive deficits in schizophrenia.