Constanze Hahn

Circadian rhythms in executive function during the transition to adolescence: the effect of synchrony between chronotype and time of day

To explore the influence of circadian rhythms on executive function during early adolescence, we administered a battery of executive function measures (including a Go-Nogo task, the Iowa Gambling Task, a Self-ordered Pointing task, and an Intra/Extradimensional Shift task) to Morning-preference and Evening-preference participants (N = 80) between the ages of 11 and 14 years who were tested in the morning or afternoon. Significant Chronotype × Time of Day interactions (controlling for amount of sleep the previous night) revealed that adolescents tested at their optimal times of day performed better than those tested at their nonoptimal times. Implications for our understanding of physiological arousal, sleep, and executive function during adolescence are discussed.

Variation in the NMDA receptor 2B subunit gene GRIN2B is associated with differential language lateralization

Variations in the N-methyl-d-aspartate receptor 2B subunit gene (GRIN2B) have been associated with schizophrenia, a psychiatric disorder associated with reduced left-hemispheric language dominance. Here, we investigated, whether different polymorphisms in GRIN2B influence language lateralization and handedness in healthy individuals. In a cohort of 424 genetically unrelated participants we found significant association between the synonymous GRIN2B variation rs1806201 and language lateralization assessed using the dichotic listening task. Individuals carrying the heterozygous CT genotype exhibited more pronounced left-hemispheric language dominance as compared to both homozygous CC and TT individuals. Such an association was not identified for handedness. These findings suggest that variation in NMDA-receptors contributes to the interindividual variability of language lateralization.

Dichotic listening revisited: trial-by-trial ERP analyses reveal intra- and interhemispheric differences.

The dichotic listening (DL) paradigm is often used to assess brain asymmetries at the behavioral level. The aim of this study was to evaluate the dynamic temporal and topographical characteristics of event related potentials (ERPs) obtained with diotic and dichotic consonant-vowel (CV) stimuli from the same subjects. We used a novel approach in which we concurrently analyzed on a trial-by-trial basis ERP parameters during trials that resulted in a right ear advantage (REA) or left ear advantage (LEA) or that were presented under diotic (homonymous) conditions. CV syllables were used as auditory stimuli (/ba/, /da/, /ga/, /ka/, /pa/, /ta/). The EEG measurements were performed with 64 channels by mainly focusing on the N1P2, N2P3 and late negativity (LN) components. Overall, behavioral data revealed a clear REA. The central area showed higher amplitudes than the other locations for N1P2 responses. Additionally, responses were faster for the diotic, compared to the dichotic conditions. The LN had shorter latencies in trials resulting in a REA, compared with those producing a LEA. This result makes it likely that the overall REA is a time-bound effect, which can be explained by the structural theory of Kimura. Furthermore, the results demonstrated a specific spatiotemporal shift from central to frontal areas between N1P2 and LN that was pronounced in dichotic trials. This shift points towards the involvement of frontal areas in resolving conflicting input.

Single-subject classification of schizophrenia by event-related potentials during selective attention

BACKGROUND Executive dysfunction has repeatedly been proposed as a robust and promising substrate of analytical approaches in the research of neurocognitive markers of schizophrenia. Here, we present a mixed model- and data-driven classification approach by applying a task that targets executive dysfunction in schizophrenia and by investigating relevant event-related potential (ERP) features with machine learning classifiers. METHODS Forty schizophrenic patients and forty matched healthy controls completed the Attention Network Test while an electroencephalogram was recorded. Target-locked N1 and P3 ERP components were constructed and submitted to different classification analyses without a priori hypotheses. Standardized source localization was applied to estimate neural sources of N1 and P3 deficits in schizophrenia. RESULTS We obtained a classification accuracy of 79% using only very few ERP components. Central P3 components following compatible and incompatible trials and right parietal N1 latencies averaged across targets and were sufficient for classification. P3 deficits were associated with anterior cingulate cortex dysfunction, while right posterior current density deficits were observed in schizophrenia during the N1 time frame. CONCLUSIONS The data exemplarily show how automated inference may be applied to classify a pathological state in single subjects without prior knowledge of their diagnoses. While classification accuracy may be optimized by application of other executive paradigms, this approach illustrates the potential of machine learning algorithms for the identification of biomarkers that are independent of clinical assessments. Conversely, data suggest a pathophysiological mechanism that includes early visual and late executive deficits during response inhibition in schizophrenia.

Evidence of specificity of a visual P3 amplitude modulation deficit in schizophrenia

BACKGROUND In a previous study, we found a reduced amplitude modulation of the visual P3 component of the event-related potential (ERP) in schizophrenic patients compared with healthy controls during inhibition in the Attention Network Test (ANT). The objective of the present study was to replicate this finding and to explore whether this cortical processing deficit is specific to schizophrenia. METHODS Sixteen schizophrenic patients, sixteen depressive patients, and sixteen healthy controls matched for age, sex, and education were included. Participants were tested with the ANT, a test of selective attention that provides behavioral estimates for alerting, orienting, and inhibition. 32-Channel electroencephalogram was recorded and visual P3 amplitudes were topographically analyzed and compared between groups. RESULTS There were no significant behavioral between-group differences in terms of mean reaction time, accuracy, and ANT effects alerting, orienting, and inhibition. Absolute visual P3 amplitude was not reduced in schizophrenia or depression. P3 amplitude modulation was defined as P3 amplitude at Pz as a function of ANT flanker conditions. We found a parietal P3 amplitude modulation deficit in schizophrenic patients (-.015) that was absent in both healthy controls (-.705; p = .002) and depressive patients (-1.022; p = .001). CONCLUSION The results provide evidence that a deficit of visual P3 amplitude modulation distinguishes schizophrenia from healthy and disease controls and provides greater discriminative power than absolute visual P3 amplitude.

Test-retest reliability of Attention Network Test measures in schizophrenia.

BACKGROUND The Attention Network Test (ANT) is a well established behavioral measure in neuropsychological research to assess three different facets of selective attention, i.e., alerting, orienting, and conflict processing. Although the ANT has been applied in healthy individuals and various clinical populations, data on retest reliability are scarce in healthy samples and lacking for clinical populations. The objective of the present study was a longitudinal assessment of relevant ANT network measures in healthy controls and schizophrenic patients. METHODS Forty-five schizophrenic patients and 55 healthy controls were tested with ANT in a test-retest design with an average interval of 7.4 months between test sessions. Test-retest reliability was analyzed with Pearson and Intra-class correlations. RESULTS Healthy controls revealed moderate to high test-retest correlations for mean reaction time, mean accuracy, conflict effect, and conflict error rates. In schizophrenic patients, moderate test-retest correlations for mean reaction time, orienting effect, and conflict effect were found. The analysis of error rates in schizophrenic patients revealed very low test-retest correlations. CONCLUSIONS The current study provides converging statistical evidence that the conflict effect and mean reaction time of ANT yield acceptable test-retest reliabilities in healthy controls and, investigated longitudinally for the first time, also in schizophrenia. Obtained differences of alerting and orienting effects in schizophrenia case-control studies should be considered more carefully. The analysis of error rates revealed heterogeneous results and therefore is not recommended for case control studies in schizophrenia.

Dissection of early bottom-up and top-down deficits during visual attention in schizophrenia

OBJECTIVE To characterize the interplay of bottom-up and top-down processing deficits of the early visual ERP component N1 in schizophrenia. METHODS Thirty-three schizophrenic patients and 61 healthy controls underwent a visual selective attention paradigm while 32-channel electroencephalogram was recorded. Visual N1 responses were calculated and source localization was applied. RESULTS Significant reductions of the cue N1 as well as the target N1 components were found in schizophrenia patients. Linear regression slopes for the cue N1 and for the cue-locked target N1 indicated significantly reduced early bottom-up and top-down modulation in patients relative to controls. Source analyses indicated that bottom-up as well as top-down N1 deficits in schizophrenia are associated with partially overlapping current density deficits in posterior cortex areas. Differential functional deficits were observed in right parietal lobe during bottom-up processing and in anterior cingulate cortex during top-down attention. CONCLUSIONS The results provide evidence for both early visual bottom-up and top-down deficits in schizophrenia and illustrate how disturbances in these processing streams converge on the visual N1 amplitude. SIGNIFICANCE Visual top-down disturbances in schizophrenia appear to be confounded by visual bottom-up deficits.

Whistled Turkish alters language asymmetries

Whistled languages represent an experiment of nature to test the widely accepted view that language comprehension is to some extent governed by the left hemisphere in a rather input-invariant manner. Indeed, left-hemisphere superiority has been reported for atonal and tonal languages, click consonants, writing and sign languages. The right hemisphere is specialized to encode acoustic properties like spectral cues, pitch, and melodic lines and plays a role for prosodic communicative cues. Would left hemisphere language superiority change when subjects had to encode a language that is constituted by acoustic properties for which the right hemisphere is specialized? Whistled Turkish uses the full lexical and syntactic information of vocal Turkish, and transforms this into whistles to transport complex conversations with constrained whistled articulations over long distances. We tested the comprehension of vocally vs. whistled identical lexical information in native whistle-speaking people of mountainous Northeast Turkey. We discovered that whistled language comprehension relies on symmetric hemispheric contributions, associated with a decrease of left and a relative increase of right hemispheric encoding mechanisms. Our results demonstrate that a language that places high demands on right-hemisphere typical acoustical encoding creates a radical change in language asymmetries. Thus, language asymmetry patterns are in an important way shaped by the physical properties of the lexical input.

Smoking modulates language lateralization in a sex-specific way

Smoking affects a widespread network of neuronal functions by altering the properties of acetylcholinergic transmission. Recent studies show that nicotine consumption affects ascending auditory pathways and alters auditory attention, particularly in men. Here we show that smoking affects language lateralization in a sex-specific way. We assessed brain asymmetries of 90 healthy, right-handed participants using a classic consonant-vowel syllable dichotic listening paradigm in a 2×3 experimental design with sex (male, female) and smoking status (non-smoker, light smoker, heavy smoker) as between-subject factors. Our results revealed that male smokers had a significantly less lateralized response pattern compared to the other groups due to a decreased response rate of their right ear. This finding suggests a group-specific impairment of the speech dominant left hemisphere. In addition, decreased overall response accuracy was observed in male smokers compared to the other experimental groups. Similar adverse effects of smoking were not detected in women. Further, a significant negative correlation was detected between the severity of nicotine dependency and response accuracy in male but not in female smokers. Taken together, these results show that smoking modulates functional brain lateralization significantly and in a sexually dimorphic manner. Given that some psychiatric disorders have been associated with altered brain asymmetries and increased smoking prevalence, nicotinergic effects need to be specifically investigated in this context in future studies.

Visual P3 amplitude modulation deficit in schizophrenia is independent of duration of illness

BACKGROUND In the search for markers of schizophrenia, functional deficits during inhibition have been a major focus. In previous studies, we found a reduced amplitude modulation of the visual P3 component of the event-related potential (ERP) in schizophrenic patients during inhibition in the Attention Network Test (ANT). The objective of the present study was to explore whether this deficit exhibits properties of a trait or state marker of schizophrenia. METHODS Eighteen recent onset inpatients and eighteen chronic schizophrenic outpatients as well as 36 healthy controls, including a young adult and an old adult group to match recent onset and chronic illness groups for age and sex, were included. Participants were tested with ANT while 32-channel electroencephalogram was recorded and visual P3 amplitudes were analyzed. Amplitude modulation was defined as the variation of P3 amplitude at Pz as a function of ANT flanker conditions. RESULTS There were no significant behavioral between-group differences in terms of alerting, orienting, and inhibition. Mean visual P3 was significantly lower in schizophrenic patients than in healthy controls. Parietal P3 amplitude was significantly less modulated in both recent onset (-0.035) and chronic schizophrenic patients (-0.081) compared with young (-0.588; p<0.05) and older healthy controls, respectively (-0.556; p<0.05). No correlations were obtained between P3 modulation and clinical or demographic variables. CONCLUSION The results provide evidence that the observed deficit of visual P3 amplitude modulation is independent of duration of illness and age and may contain properties of a trait marker of schizophrenia.