Getting the best outcomes from epilepsy surgery.

Neurosurgery is an underutilized treatment that can potentially cure drug-refractory epilepsy. Careful, multidisciplinary presurgical evaluation is vital for selecting patients and to ensure optimal outcomes. Advances in neuroimaging have improved diagnosis and guided surgical intervention. Invasive electroencephalography allows the evaluation of complex patients who would otherwise not be candidates for neurosurgery. We review the current state of the assessment and selection of patients and consider established and novel surgical procedures and associated outcome data. We aim to dispel myths that may inhibit physicians from referring and patients from considering neurosurgical intervention for drug-refractory focal epilepsies. Ann Neurol 2018;83:676-690

Correlating electroconvulsive therapy response to electroencephalographic markers: Study protocol

INTRODUCTION: Electroconvulsive therapy (ECT) is an effective intervention for patients with major depressive disorder (MDD). Despite longstanding use, the underlying mechanisms of ECT are unknown, and there are no objective prognostic biomarkers that are routinely used for ECT response. Two electroencephalographic (EEG) markers, sleep slow waves and sleep spindles, could address these needs. Both sleep microstructure EEG markers are associated with synaptic plasticity, implicated in memory consolidation, and have reduced expression in depressed individuals. We hypothesize that ECT alleviates depression through enhanced expression of sleep slow waves and sleep spindles, thereby facilitating synaptic reconfiguration in pathologic neural circuits. METHODS: Correlating ECT Response to EEG Markers (CET-REM) is a single-center, prospective, observational investigation. Wireless wearable headbands with dry EEG electrodes will be utilized for at-home unattended sleep studies to allow calculation of quantitative measures of sleep slow waves (EEG SWA, 0.5-4 Hz power) and sleep spindles (density in number/minute). High-density EEG data will be acquired during ECT to quantify seizure markers. DISCUSSION: This innovative study focuses on the longitudinal relationships of sleep microstructure and ECT seizure markers over the treatment course. We anticipate that the results from this study will improve our understanding of ECT

The anatomy of excitement:Understanding and improving the effectiveness of electroconvulsive therapy

Electroconvulsive therapy (ECT) is an effective treatment for severe depression. In this thesis, I studied electroconvulsive therapy (ECT) research with the objective to improve the clinical outcome after treatment and to gain a better understanding of its working mechanisms. Multiple methods in ECT research were explored, varying with respect to sample selection (i.e., single- versus multi-center data), study design (i.e., observational retrospective study versus prospective RCT, controlled versus non-controlled), type of data (i.e., clinical, EEG, and [f]MRI), and the applied statistical models to analyze the data (i.e., frequentist versus Bayesian models). Additionally, I proposed a taxonomy of ECT research. The main chapters can be considered as specific case-examples of the child-nodes of this taxonomy. Thereby, this thesis contributes to improving the clinical outcome and understanding of the working mechanisms of ECT. Based on the findings in this thesis, I have discussed the methods that are commonly used in ECT research and which future directions this may take

Discriminative power of EEG-based biomarkers in major depressive disorder: A systematic review

Currently, the diagnosis of major depressive disorder (MDD) and its subtypes is mainly based on subjective assessments and self-reported measures. However, objective criteria as Electroencephalography (EEG) features would be helpful in detecting depressive states at early stages to prevent the worsening of the symptoms. Scientific community has widely investigated the effectiveness of EEG-based measures to discriminate between depressed and healthy subjects, with the aim to better understand the mechanisms behind the disorder and find biomarkers useful for diagnosis. This work offers a comprehensive review of the extant literature concerning the EEG-based biomarkers for MDD and its subtypes, and identify possible future directions for this line of research. Scopus, PubMed and Web of Science databases were researched following PRISMA’s guidelines. The initial papers’ screening was based on titles and abstracts; then full texts of the identified articles were examined, and a synthesis of findings was developed using tables and thematic analysis. After screening 1871 articles, 76 studies were identified as relevant and included in the systematic review. Reviewed markers include EEG frequency bands power, EEG asymmetry, ERP components, non-linear and functional connectivity measures. Results were discussed in relations to the different EEG measures assessed in the studies. Findings confirmed the effectiveness of those measures in discriminating between healthy and depressed subjects. However, the review highlights that the causal link between EEG measures and depressive subtypes needs to be further investigated and points out that some methodological issues need to be solved to enhance future research in this field

Investigation of neural activity in Schizophrenia during resting-state MEG : using non-linear dynamics and machine-learning to shed light on information disruption in the brain

Environ 25% de la population mondiale est atteinte de troubles psychiatriques qui sont typiquement associés à des problèmes comportementaux, fonctionnels et/ou cognitifs et dont les corrélats neurophysiologiques sont encore très mal compris. Non seulement ces dysfonctionnements réduisent la qualité de vie des individus touchés, mais ils peuvent aussi devenir un fardeau pour les proches et peser lourd dans l’économie d’une société. Cibler les mécanismes responsables du fonctionnement atypique du cerveau en identifiant des biomarqueurs plus robustes permettrait le développement de traitements plus efficaces. Ainsi, le premier objectif de cette thèse est de contribuer à une meilleure caractérisation des changements dynamiques cérébraux impliqués dans les troubles mentaux, plus précisément dans la schizophrénie et les troubles d’humeur. Pour ce faire, les premiers chapitres de cette thèse présentent, en intégral, deux revues de littératures systématiques que nous avons menées sur les altérations de connectivité cérébrale, au repos, chez les patients schizophrènes, dépressifs et bipolaires. Ces revues révèlent que, malgré des avancées scientifiques considérables dans l’étude de l’altération de la connectivité cérébrale fonctionnelle, la dimension temporelle des mécanismes cérébraux à l’origine de l’atteinte de l’intégration de l’information dans ces maladies, particulièrement de la schizophrénie, est encore mal comprise. Par conséquent, le deuxième objectif de cette thèse est de caractériser les changements cérébraux associés à la schizophrénie dans le domaine temporel. Nous présentons deux études dans lesquelles nous testons l’hypothèse que la « disconnectivité temporelle » serait un biomarqueur important en schizophrénie. Ces études explorent les déficits d’intégration temporelle en schizophrénie, en quantifiant les changements de la dynamique neuronale dite invariante d’échelle à partir des données magnétoencéphalographiques (MEG) enregistrés au repos chez des patients et des sujets contrôles. En particulier, nous utilisons (1) la LRTCs (long-range temporal correlation, ou corrélation temporelle à longue-distance) calculée à partir des oscillations neuronales et (2) des analyses multifractales pour caractériser des modifications de l’activité cérébrale arythmique. Par ailleurs, nous développons des modèles de classification (en apprentissage-machine supervisé) pour mieux cerner les attributs corticaux et sous-corticaux permettant une distinction robuste entre les patients et les sujets sains. Vu que ces études se basent sur des données MEG spontanées enregistrées au repos soit avec les yeux ouvert, ou les yeux fermées, nous nous sommes par la suite intéressés à la possibilité de trouver un marqueur qui combinerait ces enregistrements. La troisième étude originale explore donc l’utilité des modulations de l’amplitude spectrale entre yeux ouverts et fermées comme prédicteur de schizophrénie. Les résultats de ces études démontrent des changements cérébraux importants chez les patients schizophrènes au niveau de la dynamique d’invariance d’échelle. Elles suggèrent une dégradation du traitement temporel de l’information chez les patients, qui pourrait être liée à leurs symptômes cognitifs et comportementaux. L’approche multimodale de cette thèse, combinant la magétoencéphalographie, analyses non-linéaires et apprentissage machine, permet de mieux caractériser l’organisation spatio-temporelle du signal cérébrale au repos chez les patients atteints de schizophrénie et chez des individus sains. Les résultats fournissent de nouvelles preuves supportant l’hypothèse d’une « disconnectivité temporelle » en schizophrénie, et étendent les recherches antérieures, en explorant la contribution des structures cérébrales profondes et en employant des mesures non-linéaires avancées encore sous-exploitées dans ce domaine. L’ensemble des résultats de cette thèse apporte une contribution significative à la quête de nouveaux biomarqueurs de la schizophrénie et démontre l’importance d’élucider les altérations des propriétés temporelles de l’activité cérébrales intrinsèque en psychiatrie. Les études présentées offrent également un cadre méthodologique pouvant être étendu à d’autres psychopathologie, telles que la dépression.Psychiatric disorders affect nearly a quarter of the world’s population. These typically bring about debilitating behavioural, functional and/or cognitive problems, for which the underlying neural mechanisms are poorly understood. These symptoms can significantly reduce the quality of life of affected individuals, impact those close to them, and bring on an economic burden on society. Hence, targeting the baseline neurophysiology associated with psychopathologies, by identifying more robust biomarkers, would improve the development of effective treatments. The first goal of this thesis is thus to contribute to a better characterization of neural dynamic alterations in mental health illnesses, specifically in schizophrenia and mood disorders. Accordingly, the first chapter of this thesis presents two systematic literature reviews, which investigate the resting-state changes in brain connectivity in schizophrenia, depression and bipolar disorder patients. Great strides have been made in neuroimaging research in identifying alterations in functional connectivity. However, these two reviews reveal a gap in the knowledge about the temporal basis of the neural mechanisms involved in the disruption of information integration in these pathologies, particularly in schizophrenia. Therefore, the second goal of this thesis is to characterize the baseline temporal neural alterations of schizophrenia. We present two studies for which we hypothesize that the resting temporal dysconnectivity could serve as a key biomarker in schizophrenia. These studies explore temporal integration deficits in schizophrenia by quantifying neural alterations of scale-free dynamics using resting-state magnetoencephalography (MEG) data. Specifically, we use (1) long-range temporal correlation (LRTC) analysis on oscillatory activity and (2) multifractal analysis on arrhythmic brain activity. In addition, we develop classification models (based on supervised machine-learning) to detect the cortical and sub-cortical features that allow for a robust division of patients and healthy controls. Given that these studies are based on MEG spontaneous brain activity, recorded at rest with either eyes-open or eyes-closed, we then explored the possibility of finding a distinctive feature that would combine both types of resting-state recordings. Thus, the third study investigates whether alterations in spectral amplitude between eyes-open and eyes-closed conditions can be used as a possible marker for schizophrenia. Overall, the three studies show changes in the scale-free dynamics of schizophrenia patients at rest that suggest a deterioration of the temporal processing of information in patients, which might relate to their cognitive and behavioural symptoms. The multimodal approach of this thesis, combining MEG, non-linear analyses and machine-learning, improves the characterization of the resting spatiotemporal neural organization of schizophrenia patients and healthy controls. Our findings provide new evidence for the temporal dysconnectivity hypothesis in schizophrenia. The results extend on previous studies by characterizing scale-free properties of deep brain structures and applying advanced non-linear metrics that are underused in the field of psychiatry. The results of this thesis contribute significantly to the identification of novel biomarkers in schizophrenia and show the importance of clarifying the temporal properties of altered intrinsic neural dynamics. Moreover, the presented studies offer a methodological framework that can be extended to other psychopathologies, such as depression

Frontal theta and posterior alpha in resting EEG: A critical examination of convergent and discriminant validity

Prior research has identified two resting EEG biomarkers with potential for predicting functional outcomes in depression: theta current density in frontal brain regions (especially rostral anterior cingulate cortex) and alpha power over posterior scalp regions. As little is known about the discriminant and convergent validity of these putative biomarkers, a thorough evaluation of these psychometric properties was conducted toward the goal of improving clinical utility of these markers. Resting 71‐channel EEG recorded from 35 healthy adults at two sessions (1‐week retest) were used to systematically compare different quantification techniques for theta and alpha sources at scalp (surface Laplacian or current source density [CSD]) and brain (distributed inverse; exact low resolution electromagnetic tomography [eLORETA]) level. Signal quality was evaluated with signal‐to‐noise ratio, participant‐level spectra, and frequency PCA covariance decomposition. Convergent and discriminant validity were assessed within a multitrait‐multimethod framework. Posterior alpha was reliably identified as two spectral components, each with unique spatial patterns and condition effects (eyes open/closed), high signal quality, and good convergent and discriminant validity. In contrast, frontal theta was characterized by one low‐variance component, low signal quality, lack of a distinct spectral peak, and mixed validity. Correlations between candidate biomarkers suggest that posterior alpha components constitute reliable, convergent, and discriminant biometrics in healthy adults. Component‐based identification of spectral activity (CSD/eLORETA‐fPCA) was superior to fixed, a priori frequency bands. Improved quantification and conceptualization of frontal theta is necessary to determine clinical utility.Magnitude of frontal theta (rostral ACC eLORETA source amplitude) and posterior alpha (spectral components of scalp current source density) at rest have been considered candidate EEG biomarkers of depression outcomes. Given inconsistent findings, we examined the discriminant and convergent validity of these measures in healthy adults. Unlike theta, two distinct alpha components constituted reliable, convergent, and discriminant biometrics. While results have marked implications for clinical utility, we make several recommendations for improving the psychometric properties of resting frontal theta.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153675/1/psyp13483.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153675/2/psyp13483_am.pd

Modern Views of Machine Learning for Precision Psychiatry

In light of the NIMH's Research Domain Criteria (RDoC), the advent of functional neuroimaging, novel technologies and methods provide new opportunities to develop precise and personalized prognosis and diagnosis of mental disorders. Machine learning (ML) and artificial intelligence (AI) technologies are playing an increasingly critical role in the new era of precision psychiatry. Combining ML/AI with neuromodulation technologies can potentially provide explainable solutions in clinical practice and effective therapeutic treatment. Advanced wearable and mobile technologies also call for the new role of ML/AI for digital phenotyping in mobile mental health. In this review, we provide a comprehensive review of the ML methodologies and applications by combining neuroimaging, neuromodulation, and advanced mobile technologies in psychiatry practice. Additionally, we review the role of ML in molecular phenotyping and cross-species biomarker identification in precision psychiatry. We further discuss explainable AI (XAI) and causality testing in a closed-human-in-the-loop manner, and highlight the ML potential in multimedia information extraction and multimodal data fusion. Finally, we discuss conceptual and practical challenges in precision psychiatry and highlight ML opportunities in future research