Test-retest reliability of the magnetic mismatch negativity response to sound duration and omission deviants

Mismatch negativity (MMN) is a neurophysiological measure of auditory novelty detection that could serve as a translational biomarker of psychiatric disorders, such as schizophrenia. However, the replicability of its magnetoencephalographic (MEG) counterpart (MMNm) has been insufficiently addressed. In the current study, test-retest reliability of the MMNm response to both duration and omission deviants was evaluated over two MEG sessions in 16 healthy adults. MMNm amplitudes and latencies were obtained at both sensor- and source-level using a cortically-constrained minimum-norm approach. Intraclass correlations (ICC) were derived to assess stability of MEG responses over time. In addition, signal-to-noise ratios (SNR) and within-subject statistics were obtained in order to determine MMNm detectability in individual participants. ICC revealed robust values at both sensor- and source-level for both duration and omission MMNm amplitudes (ICC = 0.81-0.90), in particular in the right hemisphere, while moderate to strong values were obtained for duration MMNm and omission MMNm peak latencies (ICC = 0.74-0.88). Duration MMNm was robustly identified in individual participants with high SNR, whereas omission MMNm responses were only observed in half of the participants. Our data indicate that MMNm to unexpected duration changes and omitted sounds are highly reproducible, providing support for the use of MEG-parameters in basic and clinical research

Thalamocortical synchronization and cognition: implications for schizophrenia?

Cognitive deficits are a core dysfunction in schizophrenia. In this issue of Neuron, Parnaudeau et al. (2013) investigated synchronization in thalamocortical pathways in an animal model to address the disconnection between brain regions as a mechanism for working memory impairments in the disorder.implicated dysfunctional neural oscillations in the explanation of cognitive deficits and certain clinical symptoms of schizophrenia. Specifically, we will focus on findings that have examined neural oscillations during 1) perceptual processing, 2) working memory and executive processes and 3) spontaneous activity. The importance of the development of paradigms suitable for human and animal models is discussed as well as the search for mechanistic explanation for oscillatory dysfunctions

Low-frequency oscillatory correlates of auditory predictive processing in cortical-subcortical networks: a MEG-study

Emerging evidence supports the role of neural oscillations as a mechanism for predictive information processing across large-scale networks. However, the oscillatory signatures underlying auditory mismatch detection and information flow between brain regions remain unclear. To address this issue, we examined the contribution of oscillatory activity at theta/alpha-bands (4–8/8–13 Hz) and assessed directed connectivity in magnetoencephalographic data while 17 human participants were presented with sound sequences containing predictable repetitions and order manipulations that elicited prediction-error responses. We characterized the spectro-temporal properties of neural generators using a minimum-norm approach and assessed directed connectivity using Granger Causality analysis. Mismatching sequences elicited increased theta power and phase-locking in auditory, hippocampal and prefrontal cortices, suggesting that theta-band oscillations underlie prediction-error generation in cortical-subcortical networks. Furthermore, enhanced feedforward theta/alpha-band connectivity was observed in auditory-prefrontal networks during mismatching sequences, while increased feedback connectivity in the alpha-band was observed between hippocampus and auditory regions during predictable sounds. Our findings highlight the involvement of hippocampal theta/alpha-band oscillations towards auditory prediction-error generation and suggest a spectral dissociation between inter-areal feedforward vs. feedback signalling, thus providing novel insights into the oscillatory mechanisms underlying auditory predictive processing

Gestalt perception in schizophrenia spectrum disorders.

The research examined the hypothesis that schizophrenia spectrum disorders are characterized by impairments in Gestalt perception. Participants with elevated levels of schizotypy, acute and chronic schizophrenia patients, and non-schizophrenia psychotic disorders were assessed on three measures of Gestalt perception. The hypothesis was that schizophrenia spectrum disorders are characterized by reduced responsiveness to Gestalt properties of visual stimuli. A pattern of performance on experimental tasks was predicted that would produce both impaired and enhanced task performance in schizophrenia spectrum disorders on measures of Gestalt perception. Impairments in Gestalt perception were hypothesized to correlate with symptoms of the disorganisation syndrome and with a specific aspect of social cognition, Theory of Mind (ToM), in schizophrenia spectrum disorders. The results of the research confirmed the main hypotheses. Schizophrenia spectrum disorders displayed in all studies reduced responsiveness to Gestalt properties of stimuli. Dysfunctional Gestalt perception emerged not as general feature of schizophrenia spectrums disorders, however. Cognitive deficits were specifically related to the disorganisation syndrome and statistical comparisons between participants with elevated and reduced levels of thought disorder found that dysfunctional Gestalt perception was only present in thought disordered participants with schizophrenia spectrum disorders. Dysfunctional Gestalt perception resulted consistently in both impaired and enhanced task performance in disorganised forms of schizophrenia spectrum disorders. It is concluded that the experimental results reflect a specific deficit in the perceptual organisation of stimuli based on context. Furthermore, the hypothesis was confirmed that dysfunctional Gestalt perception is correlated with impaired ToM in chronic and acute schizophrenia. The findings of the research are discussed from the perspective of recent models of cognition in schizophrenia spectrum disorders where impaired Gestalt perception is viewed as the result of a comprehensive impairment in the cognitive coordination of neural and cognitive activity. It is proposed that dysfunctional Gestalt perception may be related to a specific subtype of schizophrenia, neurodevelopmental schizophrenia, which is characterised by poor premorbid functioning, disorganised symptoms, and poor outcome. Further issues for research are discussed

Sehen, was Alzheimer nicht sah! : Demenz mit modernen bildgebenden und elektrophysiologischen Verfahren erforschen

Mit meisterhafter Präzision und einem zuverlässigen Gespür für das Außergewöhnliche seines Falles beschrieb Alois Alzheimer vor über 100 Jahren erstmals die feingeweblichen (histologischen) Veränderungen derjenigen Krankheit, die später seinen Namen tragen sollte. Gleichwohl konnte Alzheimer mithilfe des Mikroskops und der damals modernsten Färbetechniken nur wenig über den Zusammenhang zwischen den zu Lebzeiten des Patienten beobachteten Krankheitssymptomen und spezifischen Gehirnveränderungen aussagen. Heute ist zwar der histologische Befund noch immer für die zuverlässige Sicherung der Diagnose Morbus Alzheimer notwendig, aber moderne Schnittbild- sowie elektrophysiologische Verfahren erlauben es erstmals, neuroanatomische und neurofunktionelle Veränderungen zu Lebzeiten der Patienten zu erfassen. Neben ihrem unverzichtbaren Einsatz in der Ausschlussdiagnostik anderer schwerwiegender Gehirnerkrankungen wie Blutungen, Schlaganfälle und Tumore eröffnen diese Verfahren der klinischen Psychiatrie aufregende neue Forschungsperspektiven

Magnetoencephalography as a tool in psychiatric research: current status and perspective

The application of neuroimaging to provide mechanistic insights into circuit dysfunctions in major psychiatric conditions and the development of biomarkers are core challenges in current psychiatric research. In this review, we propose that recent technological and analytic advances in Magnetoencephalography (MEG), a technique which allows the measurement of neuronal events directly and non-invasively with millisecond resolution, provides novel opportunities to address these fundamental questions. Because of its potential in delineating normal and abnormal brain dynamics, we propose that MEG provides a crucial tool to advance our understanding of pathophysiological mechanisms of major neuropsychiatric conditions, such as Schizophrenia, Autism Spectrum Disorders, and the dementias. In our paper, we summarize the mechanisms underlying the generation of MEG signals and the tools available to reconstruct generators and underlying networks using advanced source-reconstruction techniques. We then survey recent studies that have utilized MEG to examine aberrant rhythmic activity in neuropsychiatric disorders. This is followed by links with preclinical research, which have highlighted possible neurobiological mechanisms, such as disturbances in excitation/inhibition parameters, which could account for measured changes in neural oscillations. In the final section of the paper, challenges as well as novel methodological developments are discussed which could pave the way for a widespread application of MEG in translational research with the aim of developing biomarkers for early detection and diagnosis

Neural synchrony in cortical networks : history, concept and current status

Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, the role of neural synchrony in cortical networks has been expanded to provide a general mechanism for the coordination of distributed neural activity patterns. In the current paper, we present an update of the status of this hypothesis through summarizing recent results from our laboratory that suggest important new insights regarding the mechanisms, function and relevance of this phenomenon. In the first part, we present recent results derived from animal experiments and mathematical simulations that provide novel explanations and mechanisms for zero and nero-zero phase lag synchronization. In the second part, we shall discuss the role of neural synchrony for expectancy during perceptual organization and its role in conscious experience. This will be followed by evidence that indicates that in addition to supporting conscious cognition, neural synchrony is abnormal in major brain disorders, such as schizophrenia and autism spectrum disorders. We conclude this paper with suggestions for further research as well as with critical issues that need to be addressed in future studies

Dissociation and Brain Rhythms: Pitfalls and Promises

Recently, Vesuna et al. proposed a novel circuit mechanism underlying dissociative states using optogenetics and pharmacology in mice in combination with intracranial recordings and electrical stimulation in an epilepsy patient. Specifically, the authors identified a posteromedial cortical delta-rhythm that underlies states of dissociation. In the following, we would like to critically review these findings in the context of the human literature on dissociation as well as highlight the challenges in translational neuroscience to link complex behavioral phenotypes in psychiatric syndromes to circumscribed circuit mechanisms

Abnormal connectional fingerprint in schizophrenia: a novel network analysis of diffusion tensor imaging data

The graph theoretical analysis of structural magnetic resonance imaging (MRI) data has received a great deal of interest in recent years to characterize the organizational principles of brain networks and their alterations in psychiatric disorders, such as schizophrenia. However, the characterization of networks in clinical populations can be challenging, since the comparison of connectivity between groups is influenced by several factors, such as the overall number of connections and the structural abnormalities of the seed regions. To overcome these limitations, the current study employed the whole-brain analysis of connectional fingerprints in diffusion tensor imaging data obtained at 3 T of chronic schizophrenia patients (n = 16) and healthy, age-matched control participants (n = 17). Probabilistic tractography was performed to quantify the connectivity of 110 brain areas. The connectional fingerprint of a brain area represents the set of relative connection probabilities to all its target areas and is, hence, less affected by overall white and gray matter changes than absolute connectivity measures. After detecting brain regions with abnormal connectional fingerprints through similarity measures, we tested each of its relative connection probability between groups. We found altered connectional fingerprints in schizophrenia patients consistent with a dysconnectivity syndrome. While the medial frontal gyrus showed only reduced connectivity, the connectional fingerprints of the inferior frontal gyrus and the putamen mainly contained relatively increased connection probabilities to areas in the frontal, limbic, and subcortical areas. These findings are in line with previous studies that reported abnormalities in striatal–frontal circuits in the pathophysiology of schizophrenia, highlighting the potential utility of connectional fingerprints for the analysis of anatomical networks in the disorder

The Audio-Visual Abnormalities Questionnaire (AVAQ): Development and validation of a new instrument for assessing anomalies in sensory perception in schizophrenia spectrum disorders

Background: Anomalies in visual and auditory perception represent an important aspect of the symptomatic manifestation of schizophrenia (ScZ). However, there are currently no instruments available that allow the assessment of the full range of auditory and visual abnormalities using a self-report measure. Methods: We developed the 85-item Audio-Visual Abnormalities Questionnaire (AVAQ) to assess abnormalities in auditory and visual processing. The AVAQ was validated in an online-sample of 355 healthy participants to establish the factorial structure, internal consistency and reliability of the instrument. In addition, participants completed the Autism-Spectrum Quotient (AQ) and the Schizotypal Personality Questionnaire (SPQ) to establish convergent validity regarding autistic and schizotypal traits. Results: High internal consistency was observed for the total AVAQ-scale (α = 0.99) as well as for the visual (α = 0.98), auditory (α = 0.96) and the audio-visual subscales (α = 0.83). Principal component analyses demonstrated one factor comprising 78 items. The AVAQ was positively correlated with the SPQ (r = 0.69, p < .001) as well as the AQ (r = 0.38, p < .001). Correlations with the SPQ were highest for unusual perceptual experiences (r = 0.72, p < .001) and lowest for social anxiety (r = 0.30, p < .001). Conclusion: The AVAQ demonstrated excellent reliability, internal consistency and construct validity. Accordingly, the instrument could be useful for characterizing sensory dysfunctions across the schizophrenia spectrum that could guide interventions as well as aid the development of biomarkers