Navigated transcranial magnetic stimulation in clinical practice and research

Navigated transcranial magnetic stimulation (nTMS) enables precise targeting of the induced electric field to selected cortical targets found by alignment of the head with a 3-D model of the subject’s brain. This is particularly important in studies of patients as some diseases, such as brain tumors, may modify the brain anatomy and function so that the external skull landmarks are not any more aligned with the brain structures. Comparison with the preoperative nTMS and intraoperative direct electrical cortical stimulation (DECS) localization of hand muscle cortical representations has given distances of 3-12 mm between the two methods. Preoperative nTMS mapping is associated with smaller craniotomies and more extensive resections of tumors. Mapping of speech areas with nTMS during videoed object naming is less specific but more sensitive than DECS and produces reliable “negative” maps: if speech nTMS does not find an active area from the area to be resected, DECS findings are highly improbable as well. The first study of clinical impact infers that speech nTMS is associated with smaller craniotomies and less postoperative speech dysfunctions. Good understanding of the relation of nTMS activation sites with those obtained by DECS adds attractivity of the use of nTMS also in the basic research of brain functions.Peer reviewe

Interictal MEG abnormalities to guide intracranial electrode implantation and predict surgical outcome

Intracranial EEG (iEEG) is the gold standard technique for epileptogenic zone (EZ) localisation, but requires a hypothesis of which tissue is epileptogenic, guided by qualitative analysis of seizure semiology and other imaging modalities such as magnetoencephalography (MEG). We hypothesised that if quantifiable MEG band power abnormalities were sampled by iEEG, then patients' post-resection seizure outcome were better. Thirty-two individuals with neocortical epilepsy underwent MEG and iEEG recordings as part of pre-surgical evaluation. Interictal MEG band power abnormalities were derived using 70 healthy controls as a normative baseline. MEG abnormality maps were compared to electrode implantation, with the spatial overlap of iEEG electrodes and MEG abnormalities recorded. Finally, we assessed if the implantation of electrodes in abnormal tissue, and resection of the strongest abnormalities determined by MEG and iEEG explained surgical outcome. Intracranial electrodes were implanted in brain tissue with the most abnormal MEG findings in individuals that were seizure-free post-resection (T=3.9, p=0.003). The overlap between MEG abnormalities and iEEG electrodes distinguished outcome groups moderately well (AUC=0.68). In isolation, the resection of the strongest MEG and iEEG abnormalities separated surgical outcome groups well (AUC=0.71, AUC=0.74 respectively). A model incorporating all three features separated outcome groups best (AUC=0.80). Intracranial EEG is a key tool to delineate the EZ and help render patients seizure-free after resection. We showed that data-driven abnormalities derived from interictal MEG recordings have clinical value and may help guide electrode placement in individuals with neocortical epilepsy. Finally, our predictive model of post-operative seizure-freedom, which leverages both MEG and iEEG recordings, may aid patient counselling of expected outcome.Comment: 22 pages, 6 figure

Sensorimotor Mapping With MEG: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines

Published: November 2020In this article, we present the clinical indications and advances in the use of magnetoencephalography to map the primary sensorimotor (SM1) cortex in neurosurgical patients noninvasively. We emphasize the advantages of magnetoencephalography over sensorimotor mapping using functional magnetic resonance imaging. Recommendations to the referring physicians and the clinical magnetoencephalographers to achieve appropriate sensorimotor cortex mapping using magnetoencephalography are proposed. We finally provide some practical advice for the use of corticomuscular coherence, corticokinematic coherence, and mu rhythm suppression in this indication. Magnetoencephalography should now be considered as a method of reference for presurgical functional mapping of the sensorimotor cortex.X. De Ti ege is Post-doctorate Clinical Master Specialist at the Fonds de la Recherche Scientifique (FRS-FNRS, Brussels, Belgium). M. Bourguignon has been supported by the program Attract of Innoviris (Grant 2015-BB2B-10), by the Spanish Ministry of Economy and Competitiveness (Grant PSI2016- 77175-P), and by the Marie Sk1odowska-Curie Action of the European Commission (Grant 743562). H. Piitulainen has been supported by the Academy of Finland (Grants #266133 and #296240), the Jane and Aatos Erkko Foundation, and the Emil Aaltonen Foundation. The authors thank Professor Riitta Hari for her support in most of the research works published by the authors and presented in this article. The MEG project at the CUB H^opital Erasme is financially supported by the Fonds Erasme (Research convention “Les Voies du Savoir,” Fonds Erasme, Brussels, Belgium)

Localization of Sensorimotor Cortex Using Navigated Transcranial Magnetic Stimulation and Magnetoencephalography

The mapping of the sensorimotor cortex gives information about the cortical motor and sensory functions. Typical mapping methods are navigated transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG). The differences between these mapping methods are, however, not fully known. TMS center of gravities (CoGs), MEG somatosensory evoked fields (SEFs), corticomuscular coherence (CMC), and corticokinematic coherence (CKC) were mapped in ten healthy adults. TMS mapping was performed for first dorsal interosseous (FDI) and extensor carpi radialis (ECR) muscles. SEFs were induced by tactile stimulation of the index finger. CMC and CKC were determined as the coherence between MEG signals and the electromyography or accelerometer signals, respectively, during voluntary muscle activity. CMC was mapped during the activation of FDI and ECR muscles separately, whereas CKC was measured during the waving of the index finger at a rate of 3-4 Hz. The maximum CMC was found at beta frequency range, whereas maximum CKC was found at the movement frequency. The mean Euclidean distances between different localizations were within 20 mm. The smallest distance was found between TMS FDI and TMS ECR CoGs and longest between CMC FDI and CMC ECR sites. TMS-inferred localizations (CoGs) were less variable across participants than MEG-inferred localizations (CMC, CKC). On average, SEF locations were 8 mm lateral to the TMS CoGs (p <0.01). No differences between hemispheres were found. Based on the results, TMS appears to be more viable than MEG in locating motor cortical areas.Peer reviewe

The role of neuronavigation in TMS-EEG studies : Current applications and future perspectives

Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) allows measuring noninvasively the electrical response of the human cerebral cortex to a direct perturbation. Complementing TMSEEG with a structural neuronavigation tool (nTMS-EEG) is key for accurately selecting cortical areas, targeting them, and adjusting the stimulation parameters based on some relevant anatomical priors. This step, together with the employment of visualization tools designed to perform a quality check of TMS-evoked potentials (TEPs) in real-time during TMS-EEG data acquisition, is pivotal for maximizing the impact of the TMS pulse on the cortex and in ensuring highly reproducible measurements within sessions and across subjects. Moreover, storing stimulation parameters in the neumnavigation system can help in replicating the stimulation parameters within and across experimental sessions and sharing them across research centers. Finally, the systematic employment of neumnavigation in TMS-EEG studies is also critical to standardize measurements in clinical populations in search for reliable diagnostic and prognostic TMS-EEG-based biomarkers for neurological and psychiatric disorders.Peer reviewe

Pre-surgical mapping of eloquent cortex for paediatric epilepsy surgery candidates: Evidence from a review of advanced functional neuroimaging

Purpose: A review of all published evidence for mapping eloquent (motor, language and memory) cortex using advanced functional neuroimaging (functional magnetic resonance imaging [fMRI] and magnetoencephalography [MEG]) for paediatric epilepsy surgery candidates has not been conducted previously. Research in this area has predominantly been in adult populations and applicability of these techniques to paediatric populations is less established. Methods: A review was performed using an advanced systematic search and retrieval of all published papers examining the use of functional neuroimaging for paediatric epilepsy surgery candidates. Results: Of the 2,724 papers retrieved, 34 met the inclusion criteria. Total paediatric participants identified were 353 with an age range of 5 months-19 years. Sample sizes and comparisons with alternative investigations to validate techniques are small and variable paradigms are used. Sensitivity 0.72 (95% CI 0.52-0.86) and specificity 0.60 (95% CI 0.35-0.92) values with a Positive Predictive Value of 74% (95% CI 61-87) and a Negative Predictive Value of 65% (95% CI 52-78) for fMRI language lateralisation with validation, were obtained. Retrieved studies indicate evidence that both fMRI and MEG are able to provide information lateralising and localising motor and language functions. Conclusions: A striking finding of the review is the paucity of studies (n = 34) focusing on the paediatric epilepsy surgery population. For children, it remains unclear which language and memory paradigms produce optimal activation and how these should be quantified in a statistically robust manner. Consensus needs to be achieved for statistical analyses and the uniformity and yield of language, motor and memory paradigms. Larger scale studies are required to produce patient series data which clinicians may refer to interpret results objectively. If functional imaging techniques are to be the viable alternative for pre-surgical mapping of eloquent cortex for children, paradigms and analyses demonstrating concordance with independent measures must be developed

Operationsplanung eloquenter Hirntumoren – vom inoperablen zum operablen Hirntumor

Auf Grundlage der vorliegenden Habilitationsschrift kann der Begriff des motorisch- und Sprach-eloquenten Hirntumors nunmehr objektiviert und genauer charakterisiert werden. Bei Patientinnen und Patienten mit bislang als inoperabel eingeschätzten Hirntumoren kann unter Einsatz der nTMS und der nTMS-basierten DTI-Traktografie eine differenziertere Abwägung zwischen Operationsrisiko und möglichem onkologischem Benefit einer Hirntumorresektion erfolgen. Die Standardisierung der Pyramidenbahn-Traktografie im Rahmen der ersten Studie verbesserte mit Integration der funktionellen nTMS-Daten die Traktografie-Qualität und zeichnete sich zudem durch eine ausgezeichnete Interrater-Reliabilität aus. Eine beeinträchtigte Integrität der peritumoralen Pyramidenbahn kann durch die Diffusionsparameter FA und ADC charakterisiert werden und war mit einem erhöhten Risiko für ein neues postoperatives motorisches Defizit assoziiert. Die Erkenntnisse der ersten Arbeit wurden mit Analysen zuvor publizierter Arbeiten genutzt, um in der zweiten Studie die nTMS-basierte Risikostratifizierung bizentrisch zu validieren. Neben der topografischen Analyse (Infiltration des Motorkortex und Bestimmung der Tumor- Trakt-Distanz) erwiesen sich die FA und der RMT, welche die Faserbahnintegrität bzw. die Exzitabilität des motorischen System repräsentieren, als entscheidende Parameter zur V orhersage des Operationsrisikos. So konnte ein verbessertes, auf einer Regressionsbaumanalyse basierendes Risikomodell zur Vorhersage des kurz- und langfristigen motorischen Outcomes entwickelt werden. Im Rahmen der dritten Studie konnte gezeigt werden, dass die präoperative Risikoanalyse die Durchführung des IOMs unterstützen kann, indem subkortikale Stimulationsintensitäten angepasst und unspezifische Phänomene wie transiente/partielle MEP- Amplitudenminderungen differenzierter interpretiert werden können. Somit kann eine hoch individualisierte Behandlungsstrategie für Patientinnen und Patienten mit motorisch- eloquenten Hirntumoren gewährleistet werden. Für die Beurteilung Sprach-eloquenter Hirntumoren kommen sowohl das kortikale rTMS- Sprachmapping (als Negativmapping) sowie die DTI-basierte Traktografie des Sprachnetzwerks zum Einsatz. In der vierten Arbeit offenbarte der Vergleich aller bisher publizierten Algorithmen, dass die Platzierung anatomischer ROIs die besten Traktografie- Ergebnisse hinsichtlich der Darstellbarkeit und Plausibilität der Trakte offenbarte. Dieser Algorithmus wurde von internationalen Experten auch zur Operationsplanung und für das Risiko-Assessment bevorzugt. Die Integration funktioneller rTMS-basierter ROIs ermöglichte die zusätzliche Darstellung von kortiko-subkortikalen Fasern, deren Relevanz für das Sprachoutcome es in weiteren Studien zu untersuchen gilt. Die Cluster-Analyse der fünften Studie identifizierte zwei Hochrisikoareale, die mit dem Auftreten eines neuen postoperativen Sprachdefizits assoziiert waren: 1. die temporo-parieto- occipitale Übergangszone und 2. der Temporalstamm der periinsulären weißen Substanz. Der AF als V ertreter des dorsalen Systems zeigte sich als wichtigste Faserbahn für die Sprachfunktion, deren Verletzung mit dem höchsten Risiko für eine postoperative Sprachstörung assoziiert war. Eine Schädigung des ventralen Faserbahnsystems spielte vor allem dann für das postoperative Sprachoutcome eine Rolle, wenn sowohl die direkte Bahn (IFOF) als auch der indirekte Kreislauf (UF und ILF) betroffen waren. Die hier dargelegten Technologien der nTMS und DTI-Traktografie ermöglichen für motorisch- und Sprach-eloquente Hirntumoren eine differenzierte und individuelle Operationsplanung. Ziel zukünftiger Arbeiten wird es sein, diese Technologien weiter zu optimieren, um Hirntumoroperationen sicherer zu gestalten und damit die individuelle Patientenbehandlung zu verbessern

Cortical mapping of the neuronal circuits modulating the muscle tone. Introduction to the electrophysiological treatment of the spastic hand

L'objectiu d'aquest estudi es investigar l'organització cortical junt amb la connectivitat còrtico-subcortical en subjectes sans, com a estudi preliminar. Els mapes corticals s'han fet per TMS navegada, i els punts motors obtinguts s'han exportant per estudi tractogràfic i anàlisi de las seves connexions. El coneixement precís de la localització de l'àrea cortical motora primària i les seves connexions es la base per ser utilitzada en estudis posteriors de la reorganització cortical i sub-cortical en pacients amb infart cerebral. Aquesta reorganització es deguda a la neuroplasticitat i pot ser influenciada per els efectes neuromoduladors de la estimulació cerebral no invasiva.The purpose of this study is to investigate the motor cortex organisation together with the cortico-subcortical connectivity in healthy subjects, as a preliminary study. Cortical maps have been performed by navigated TMS and the motor points have been exported to DTI to study their subcortical connectivity. The precise knowledge of localization of the primary motor cortex area and its connectivity is the base to be used in later studies of cortical and subcortical re-organisation in stroke patients. This re-organisation is due to the neuroplascity and can be influenced by the neuromodulation effects of the non-invasive cerebral stimulation therapy by TMS