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

High-frequency neural oscillations and visual processing deficits in schizophrenia

Visual information is fundamental to how we understand our environment, make predictions, and interact with others. Recent research has underscored the importance of visuo-perceptual dysfunctions for cognitive deficits and pathophysiological processes in schizophrenia. In the current paper, we review evidence for the relevance of high frequency (beta/gamma) oscillations towards visuo-perceptual dysfunctions in schizophrenia. In the first part of the paper, we examine the relationship between beta/gamma band oscillations and visual processing during normal brain functioning. We then summarize EEG/MEG-studies which demonstrate reduced amplitude and synchrony of high-frequency activity during visual stimulation in schizophrenia. In the final part of the paper, we identify neurobiological correlates as well as offer perspectives for future research to stimulate further inquiry into the role of high-frequency oscillations in visual processing impairments in the disorder

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

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

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

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

Neuronal assembly dynamics in supervised and unsupervised learning scenarios

The dynamic formation of groups of neurons—neuronal assemblies—is believed to mediate cognitive phenomena at many levels, but their detailed operation and mechanisms of interaction are still to be uncovered. One hypothesis suggests that synchronized oscillations underpin their formation and functioning, with a focus on the temporal structure of neuronal signals. In this context, we investigate neuronal assembly dynamics in two complementary scenarios: the first, a supervised spike pattern classification task, in which noisy variations of a collection of spikes have to be correctly labeled; the second, an unsupervised, minimally cognitive evolutionary robotics tasks, in which an evolved agent has to cope with multiple, possibly conflicting, objectives. In both cases, the more traditional dynamical analysis of the system’s variables is paired with information-theoretic techniques in order to get a broader picture of the ongoing interactions with and within the network. The neural network model is inspired by the Kuramoto model of coupled phase oscillators and allows one to fine-tune the network synchronization dynamics and assembly configuration. The experiments explore the computational power, redundancy, and generalization capability of neuronal circuits, demonstrating that performance depends nonlinearly on the number of assemblies and neurons in the network and showing that the framework can be exploited to generate minimally cognitive behaviors, with dynamic assembly formation accounting for varying degrees of stimuli modulation of the sensorimotor interactions

Impairment in predictive processes during auditory mismatch negativity in ScZ: evidence from event-related fields

Patients with schizophrenia (ScZ) show pronounced dysfunctions in auditory perception but the underlying mechanisms as well as the localization of the deficit remain unclear. To examine these questions, the current study examined whether alterations in the neuromagnetic mismatch negativity (MMNm) in ScZ-patients could involve an impairment in sensory predictions in local sensory and higher auditory areas. Using a whole-head MEG-approach, we investigated the MMNm as well as P300m and N100m amplitudes during a hierarchical auditory novelty paradigm in 16 medicated ScZ-patients and 16 controls. In addition, responses to omitted sounds were investigated, allowing for a critical test of the predictive coding hypothesis. Source-localization was performed to identify the generators of the MMNm, omission responses as well as the P300m. Clinical symptoms were examined with the positive and negative syndrome scale. Event-related fields (ERFs) to standard sounds were intact in ScZ-patients. However, the ScZ-group showed a reduction in the amplitude of the MMNm during both local (within trials) and global (across trials) conditions as well as an absent P300m at the global level. Importantly, responses to sound omissions were reduced in ScZ-patients which overlapped both in latency and generators with the MMNm sources. Thus, our data suggest that auditory dysfunctions in ScZ involve impaired predictive processes that involve deficits in both automatic and conscious detection of auditory regularities

Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

Techniques pour améliorer l’attention et l’engagement dans le traitement des patients souffrant de schizophrénie avec de graves déficits cognitifs (troisième partie)

Malgré l’existence de plusieurs interventions psychiatriques de groupe efficaces, beaucoup de patients gravement atteints sont incapables d’en bénéficier en raison de leur incapacité à maintenir leur attention lors des sessions de groupe. L’inattention pourrait être due à un ou plusieurs facteurs, dont un déficit d’attention, une faible motivation, aux effets sédatifs de la médication, et aux hallucinations et pensées troublantes dont l’effet interfère. Les interventions typiques de réhabilitation cognitive existantes pour la schizophrénie n’abordent pas ces facteurs, mais ciblent les fonctions de haut niveau comme la mémoire, l’apprentissage, la résolution de problèmes et le fonctionnement exécutif. Dans cet article, les auteurs décrivent des techniques qui insistent sur l’attention et l’engagement des patients gravement atteints et réfractaires aux traitements. Ces techniques concernent à la fois les interventions individuelles et les interventions de groupe.While many effective group-based psychiatric rehabilitation interventions now exist, many severely disabled patients are unable to benefit from them due to a reduced ability to pay attention in group sessions. Moreover, inattentiveness can be due to one or more of multiple factors, including a sustained attention deficit, poor motivation, sedating side effects of medication, and the interfering effects of hallucinations and disturbing thoughts. Existing cognitive rehabilitation interventions for schizophrenia typically do not address these factors, instead targeting higher level functions such as memory, learning, problem-solving, and executive functioning. In this paper, we describe techniques for promoting attentiveness and treatment engagement among severely disabled “treatment-refractory” patients. This includes both individual and group-based interventions.A pesar de la existencia de varias intervenciones psiquiátricas de grupos eficaces, muchos pacientes gravemente afectados son incapaces de beneficiarse con ellas debido a su incapacidad de mantener la atención durante las sesiones de grupo. La falta de atención podría deberse a uno o varios factores, entre ellos a un déficit de atención, una motivación débil, los efectos sedativos de la medicación y las alucinaciones y pensamientos perturbadores cuyo efecto interfiere. Las intervenciones típicas de rehabilitación cognitiva existentes para la esquizofrenia no abordan estos factores, pero se enfocan en las funciones de nivel elevado como la memoria, el aprendizaje, la resolución de problemas y el funcionamiento ejecutivo. En este artículo, los autores describen las técnicas que insisten en la atención y la implicación de los pacientes gravemente afectados y refractarios a los tratamientos. Estas técnicas conciernen a la vez a las intervenciones individuales y a las intervenciones de grupo.Apesar da existência de várias intervenções psiquiátricas de grupo eficazes, muitos pacientes gravemente atingidos são incapazes de usufruir destas intervenções por causa de sua incapacidade em manter a atenção durante sessões de grupo. A falta de atenção poderia ser devida a um ou vários fatores, entre eles a um déficit de atenção, a uma baixa motivação, aos efeitos sedativos da medicação e às alucinações e pensamentos perturbadores cujo efeito pode interferir no tratamento. As intervenções típicas de reabilitação cognitiva existentes para a esquizofrenia não abordam estes fatores, mas visam as funções de alto nível como a memória, a aprendizagem, a resolução de problemas e o funcionamento executivo. Neste artigo, os autores descrevem técnicas que insistem na atenção e no empenho dos pacientes gravemente atingidos e refratários aos tratamentos. Estas técnicas tratam ao mesmo tempo das intervenções individuais e das intervenções de grupo