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

The role of temporal contingency and integrity of visual inputs in the sense of agency: A psychophysical study

The sense of agency is a subjective feeling that one's own actions drive action outcomes. Previous studies have focused primarily on the temporal contingency between actions and sensory inputs as a possible mechanism for the sense of agency. However, the contribution of the integrity of visual inputs has not been systematically addressed. In the current study, we developed a psychophysical task to examine the role of visual inputs as well as temporal contingencies toward the sense of agency. Specifically, participants were required to track a target on a sinusoidal curve on a computer screen. Visual integrity of sensory inputs was manipulated by gradually occluding a computer cursor, and participants were asked to report the sense of agency on a nine-point Likert scale. Temporal contingency was manipulated by varying the delay between finger movements on a touchpad and cursor movements. The results showed that the sense of agency was influenced by both visual integrity and temporal contingency. These results are discussed in the context of current models that have proposed that the sense of agency emerges from the comparison of visual inputs with motor commands

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

Digital tools for youth mental health.

No abstract available

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