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

A pragmatic cluster randomised controlled trial of an oral health intervention for people with serious mental illness (three shires early intervention dental trial).

People with mental illness have poor oral health compared to those without due to medication side effects, issues with self-care, barriers to treatment and poor recognition of dental problems. Guidelines recommend giving oral health advice and monitoring oral health for people with mental illness, but this is not reflected in current practice and Cochrane reviews found no existing randomised trials of these interventions

The Sunyaev-Zel'dovich temperature of the intracluster medium

The relativistic Sunyaev-Zel'dovich (SZ) effect offers a method, independent of X-ray, for measuring the temperature of the intracluster medium (ICM) in the hottest systems. Here, using N-body/hydrodynamic simulations of three galaxy clusters, we compare the two quantities for a non-radiative ICM, and for one that is subject both to radiative cooling and strong energy feedback from galaxies. Our study has yielded two interesting results. Firstly, in all cases, the SZ temperature is hotter than the X-ray temperature and is within ten per cent of the virial temperature of the cluster. Secondly, the mean SZ temperature is less affected by cooling and feedback than the X-ray temperature. Both these results can be explained by the SZ temperature being less sensitive to the distribution of cool gas associated with cluster substructure. A comparison of the SZ and X-ray temperatures (measured for a sample of hot clusters) would therefore yield interesting constraints on the thermodynamic structure of the intracluster gas.Comment: This version accepted for publication in MNRAS following minor revisio

Clinical Utility of Machine-Learning Approaches in Schizophrenia: Improving Diagnostic Confidence for Translational Neuroimaging

Machine-learning approaches are becoming commonplace in the neuroimaging literature as potential diagnostic and prognostic tools for the study of clinical populations. However, very few studies provide clinically informative measures to aid in decision-making and resource allocation. Head-to-head comparison of neuroimaging-based multivariate classifiers is an essential first step to promote translation of these tools to clinical practice. We systematically evaluated the classifier performance using back-to-back structural MRI in two field strengths (3- and 7-T) to discriminate patients with schizophrenia (n = 19) from healthy controls (n = 20). Gray matter (GM) and white matter images were used as inputs into a support vector machine to classify patients and control subjects. Seven Tesla classifiers outperformed the 3-T classifiers with accuracy reaching as high as 77% for the 7-T GM classifier compared to 66.6% for the 3-T GM classifier. Furthermore, diagnostic odds ratio (a measure that is not affected by variations in sample characteristics) and number needed to predict (a measure based on Bayesian certainty of a test result) indicated superior performance of the 7-T classifiers, whereby for each correct diagnosis made, the number of patients that need to be examined using the 7-T GM classifier was one less than the number that need to be examined if a different classifier was used. Using a hypothetical example, we highlight how these findings could have significant implications for clinical decision-making. We encourage the reporting of measures proposed here in future studies utilizing machine-learning approaches. This will not only promote the search for an optimum diagnostic tool but also aid in the translation of neuroimaging to clinical use

Adiabatic and isocurvature fluctuations of Affleck-Dine field in D-term inflation model

We reconsider fluctuations of Affleck-Dine (AD) field in a D-term inflation model. Contrary to the previous analysis, we find that the spectrum of the adiabatic fluctuations is almost scale invariant even if the AD field has a large initial value. Furthermore, we study the isocurvature fluctuations of the AD field and estimate the ratio of the isocurvature to adiabatic power spectrum. The dynamics of the inflaton and AD fields sets the upper bound for the value of the AD field, leading to a lower limit for isocurvature perturbation. It is shown that the recent Cosmic Microwave Background data give a constraint on the D-term inflation and the AD field.Comment: 11pages,2figures;to appear in Phys. Lett.

The Core Deficit of Classical Schizophrenia: Implications for Predicting the Functional Outcome of Psychotic Illness and Developing Effective Treatments

© The Author(s) 2019. Many people suffering from psychotic illnesses experience persisting impairment of occupational and social function. Evidence assembled since the classical description of schizophrenia over a century ago indicates that both disorganization and impoverishment of mental activity are associated with persisting impairment. Longitudinal studies of young people at risk of schizophrenia reveal that both mental impoverishment and disorganization predict poor long-term outcome. These clinical features are related to cognitive impairments. Evidence from brain imaging indicates overlap in the brain abnormalities implicated in these phenomena, including impaired function of long-range connections between sensory cortex and the salience network, a network engaged in recruiting cerebral systems for processing of information salient to current circumstances. The evidence suggests that the common features underlying these two groups of symptoms might reflect a core pathological process distinguishing nonaffective from affective psychosis. This pathological process might therefore justifiably be designated the “core deficit” of classical schizophrenia. To develop more effective treatments to prevent persisting disability, we require the ability to identify individuals at risk at an early stage. Recent studies provide pointers toward effective strategies for identifying cases at risk of poor outcome. Accumulating evidence confirms that appreciable potential for neuroplastic change in the brain persists into adult life. Furthermore, brain function can be enhanced by targeted neuromodulation treatments. We now have promising tools not only for investigating the psychological and neural mechanisms that underlie persisting functional impairment but also for identifying individuals at risk and for harnessing brain plasticity to improve treatment

Abnormalities in structural covariance of cortical gyrification in schizophrenia

The highly convoluted shape of the adult human brain results from several well-coordinated maturational events that start from embryonic development and extend through the adult life span. Disturbances in these maturational events can result in various neurological and psychiatric disorders, resulting in abnormal patterns of morphological relationship among cortical structures (structural covariance). Structural covariance can be studied using graph theory-based approaches that evaluate topological properties of brain networks. Covariance-based graph metrics allow cross-sectional study of coordinated maturational relationship among brain regions. Disrupted gyrification of focal brain regions is a consistent feature of schizophrenia. However, it is unclear if these localized disturbances result from a failure of coordinated development of brain regions in schizophrenia. We studied the structural covariance of gyrification in a sample of 41 patients with schizophrenia and 40 healthy controls by constructing gyrification-based networks using a 3-dimensional index. We found that several key regions including anterior insula and dorsolateral prefrontal cortex show increased segregation in schizophrenia, alongside reduced segregation in somato-sensory and occipital regions. Patients also showed a lack of prominence of the distributed covariance (hubness) of cingulate cortex. The abnormal segregated folding pattern in the right peri-sylvian regions (insula and fronto-temporal cortex) was associated with greater severity of illness. The study of structural covariance in cortical folding supports the presence of subtle deviation in the coordinated development of cortical convolutions in schizophrenia. The heterogeneity in the severity of schizophrenia could be explained in part by aberrant trajectories of neurodevelopment

Immediate effects of risperidone on cerebral activity in healthy subjects: a comparison with subjects with firstepisode schizophrenia

Objective: To test the hypothesis that administration of risperidone to healthy subjects produces reductions in metabolism in the frontal cortex similar to those produced by administration of risperidone to patients experiencing a first episode of schizophrenia. Methods: Positron emission tomography was used to measure the changes in regional metabolism produced by a single 2-mg dose of risperidone and by placebo, administered under randomized, double-blind conditions, in 9 healthy subjects. Conjunction analysis was used to identify those cerebral sites where changes in metabolism in the healthy subjects coincided with similar changes in metabolism observed in patients with schizophrenia. Results: Compared with placebo, risperidone produced reductions in metabolism in the left lateral frontal cortex and right medial frontal cortex in healthy subjects. Conjunction analysis revealed that these changes occurred at locations similar to the loci of change produced by risperidone in patients with schizophrenia. Conclusion: Because the reduction in metabolism in the medial frontal cortex produced by risperidone is associated with alleviation of positive symptoms in patients with schizophrenia, the observation of a reduction in metabolism at a similar site in healthy subjects supports the hypothesis that the antipsychotic effect of risperidone arises, at least in part, from a physiologic effect that occurs in both patients with schizophrenia and healthy subjects. Objectif : Vérifier l'hypothèse selon laquelle l'administration de rispéridone à des sujets en bonne santé provoque, dans le cortex frontal, des baisses du métabolisme semblables à celles que produit l'administration de rispéridone à des patients victimes d'une première crise de schizophrénie. Méthodes : On a utilisé la tomographie par émission de positrons pour mesurer les changements du métabolisme régional produits par une seule dose de 2 mg de rispéridone et par un placebo, administrée à neuf sujets en bonne santé dans des conditions randomisées et à double insu. On a eu recours à l'analyse de corrélation pour identifier les sites du cerveau où des changements du métabolisme chez les sujets en bonne santé ont coïncidé avec des changements semblables du métabolisme observés chez des patients atteints de schizophrénie. Résultats : Comparativement au placebo, la rispéridone a produit des réductions du métabolisme dans l

Task-related default mode network modulation and inhibitory control in ADHD: effects of motivation and methylphenidate

Background: Deficits characteristic of Attention Deficit/Hyperactivity Disorder (ADHD), including poor attention and inhibitory control, are at least partially alleviated by factors that increase engagement of attention, suggesting a hypodopaminergic reward deficit. Lapses of attention are associated with attenuated deactivation of the Default Mode Network (DMN), a distributed brain system normally deactivated during tasks requiring attention to the external world. Task-related DMN deactivation has been shown to be attenuated in ADHD relative to controls. We hypothesised that motivational incentives to balance speed against restraint would increase task engagement during an inhibitory control task, enhancing DMN deactivation in ADHD. We also hypothesised that methylphenidate, an indirect dopamine agonist, would tend to normalise abnormal patterns of DMN deactivation. Method: We obtained functional magnetic resonance images from eighteen methylphenidate-responsive children with ADHD (DSM-IV combined subtype) and 18 pairwise-matched typically developing children aged 9-15 years while they performed a paced Go/No-go task. We manipulated motivational incentive to balance response speed against inhibitory control, and tested children with ADHD both on and off methylphenidate. Results: When children with ADHD were off-methylphenidate and task incentive was low, event-related DMN deactivation was significantly attenuated compared to controls, but the two groups did not differ under high motivational incentives. The modulation of DMN deactivation by incentive in the children with ADHD, off- methylphenidate, was statistically significant, and significantly greater than in typically developing children. When children with ADHD were on-methylphenidate, motivational modulation of event-related DMN deactivation was abolished, and no attenuation relative to their typically developing peers was apparent in either motivational condition. Conclusions: During an inhibitory control task, children with ADHD exhibit a raised motivational threshold at which task-relevant stimuli become sufficiently salient to deactivate the DMN. Treatment with methylphenidate normalises this threshold, rendering their pattern of task-related DMN deactivation indistinguishable from that of typically developing children

Cortical folding and the potential for prognostic neuroimaging in schizophrenia

In 41 patients with schizophrenia, we used neuroanatomical information derived from structural imaging to identify patients with more severe illness, characterised by high symptom burden, low processing speed, high degree of illness persistence and lower social and occupational functional capacity. Cortical folding, but not thickness or volume, showed a high discriminatory ability in correctly identifying patients with more severe illness