Protocol for motor and language mapping by navigated TMS in patients and healthy volunteers; workshop report

Navigated transcranial magnetic stimulation (nTMS) is increasingly used for preoperative mapping of motor function, and clinical evidence for its benefit for brain tumor patients is accumulating. In respect to language mapping with repetitive nTMS, literature reports have yielded variable results, and it is currently not routinely performed for presurgical language localization. The aim of this project is to define a common protocol for nTMS motor and language mapping to standardize its neurosurgical application and increase its clinical value. The nTMS workshop group, consisting of highly experienced nTMS users with experience of more than 1500 preoperative nTMS examinations, met in Helsinki in January 2016 for thorough discussions of current evidence and personal experiences with the goal to recommend a standardized protocol for neurosurgical applications. nTMS motor mapping is a reliable and clinically validated tool to identify functional areas belonging to both normal and lesioned primary motor cortex. In contrast, this is less clear for language-eloquent cortical areas identified by nTMS. The user group agreed on a core protocol, which enables comparison of results between centers and has an excellent safety profile. Recommendations for nTMS motor and language mapping protocols and their optimal clinical integration are presented here. At present, the expert panel recommends nTMS motor mapping in routine neurosurgical practice, as it has a sufficient level of evidence supporting its reliability. The panel recommends that nTMS language mapping be used in the framework of clinical studies to continue refinement of its protocol and increase reliability.Peer reviewe

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

Bihemispheric Navigated Transcranial Magnetic Stimulation Mapping for Action Naming Compared to Object Naming in Sentence Context

Preoperative language mapping with navigated transcranial magnetic stimulation (nTMS) is currently based on the disruption of performance during object naming. The resulting cortical language maps, however, lack accuracy when compared to intraoperative mapping. The question arises whether nTMS results can be improved, when another language task is considered, involving verb retrieval in sentence context. Twenty healthy German speakers were tested with object naming and a novel action naming task during nTMS language mapping. Error rates and categories in both hemispheres were compared. Action naming showed a significantly higher error rate than object naming in both hemispheres. Error category comparison revealed that this discrepancy stems from more lexico-semantic errors during action naming, indicating lexico-semantic retrieval of the verb being more affected than noun retrieval. In an area-wise comparison, higher error rates surfaced in multiple right-hemisphere areas, but only trends in the left ventral postcentral gyrus and middle superior temporal gyrus. Hesitation errors contributed significantly to the error count, but did not dull the mapping results. Inclusion of action naming coupled with a detailed error analysis may be favorable for nTMS mapping and ultimately improve accuracy in preoperative planning. Moreover, the results stress the recruitment of both left- and right-hemispheric areas during naming

Navigoidun transkraniaalisen magneettistimulaation käyttö ennen leikkausta tehtävissä toiminnallisten aivokuorialueiden kartoituksissa epilepsiapotilailla

Individually navigated transcranial magnetic stimulation (nTMS) has been used to locate and map the primary motor cortical areas since the inception of the technique. Recently, it has been added to the pre-surgical routine for epilepsy and brain tumor patients. The accuracy of the mappings in healthy volunteers and brain tumor patients and their feasibility in the pre-surgical evaluation of brain tumor patients have been established. The originating causes for epilepsy are variable and affect the functional localizations in relation to conventional anatomy. A reliable and versatile pre-surgical method for the localization of the functional cortical areas is essential for pre-surgical risk-benefit assessments and it is important to the success of surgical treatments. In this thesis, I describe an nTMS mapping protocol suitable for clinical use and evaluate the accuracy of the motor cortical mappings by comparing the results with the results of direct electrical stimulation of the primary motor cortex. The accuracy, 11 ± 4 mm for the hand and 16 ± 7 mm for the arm muscle groups, is sufficiently good for pre-surgical evaluation in patients with severe epilepsy. With this patient group, the nTMS technique enables the mapping of the abnormally excitable tissue, which has an impact on the interpretation and reliability of the mappings as well. In addition to the mapping of the motor cortical areas, the cortical areas related to speech are of key interest in neurosurgery. The speech-related cortical areas are commonly localized noninvasively with functional magnetic resonance imaging techniques. The dominant hemisphere for language functions can be discriminated with the invasive Wada test in the pre- surgical evaluation of epilepsy patients. Recently, nTMS protocols have been introduced for localization of speech-related cortical areas. The analysis of the nTMS elicited modifications in the language task performance have commonly been analyzed manually from video recordings and the methods for the reliable determination of the nTMS elicited speech-response latencies, their categorization and analysis, have been sparse. In the last part of this dissertation, I developed a semi-automated script for the speech-response latency difference calculation based on the accelerometer signal of the speech-response elicited vibrations of the larynx. The developed script was individually optimized for speech-response detection. According to the presented results the method is capable of determining the speech-response latencies with a sensitivity of 96% and a specificity of 71%, against the manual review from the video and visual observations from the accelerometer signals. Based on the results presented in this thesis, nTMS is a reliable method for the mapping of the functional cortical areas pre-surgically in patients with severe epilepsy. It also enables the mapping of abnormally excitable brain areas.Yksilöllisesti navigoitua transkraniaalista magneettistimulaatiota (nTMS) on käytetty koko menetelmän olemassaolon ajan liikeaivokuoren tarkkaan paikantamiseen, ja viime vuosina menetelmää on ryhdytty käyttämään rutiininomaisesti ennen kirurgista hoitoa epilepsia- ja aivokasvainpotilailla. nTMS-kartoitusten luotettavuus terveillä koehenkilöillä on vakiintunut ja kartoitusten on todettu olevan käyttökelpoisia aivokasvainpotilailla leikkaushoidon suunnittelussa. Vaikeaa epilepsiaa sairastavilla potilailla kohtausten alkusyy voi vaihdella suuresti, millä voi olla vaikutusta aivokuoren toiminnallisten alueiden sijaintiin suhteessa tavanomaiseen anatomiaan. Riittävän monipuolinen ja luotettava toiminnallisten alueiden kartoitus ennen leikkauksen riski-hyötyarviointia ja leikkauspäätöstä on hyödyllistä hoidon onnistumisen kannalta. Tässä väitöskirjatyössä esittelen kliiniseen työhön soveltuvan epilepsiapotilaiden liikeaivokuoren paikannusprotokollan ja osoitan protokollalla saatujen nTMS-kartoitustulosten tarkkuuden vastaavan aivokuoren pinnalta tehtyjen suorien sähköstimulaatioiden tuloksia. Menetelmän tarkkuuden voidaan todeta olevan riittävä leikkaushoidon suunnitteluun vaikeaa epilepsiaa sairastavilla potilailla. nTMS-menetelmällä on mahdollista paikantaa myös epilepsiaa sairastavien potilaiden poikkeavasti ärtyviä aivokuoren alueita. Tällä on merkitystä kartoitustuloksia tulkittaessa ja niiden luotettavuutta arvioitaessa, samoin kuin kirurgisesti poistettavan alueen laajuutta ja kohdennusta määritettäessä. Epilepsiaa sairastavien potilaiden liikeaivokuoren paikantamisen lisäksi mielenkiinnon kohteena on puheen tuottamiseen ja käsittelyyn liittyvien aivokuorialueiden paikannus. Näitä aivokuoren alueita paikannetaan tyypillisesti toiminnallisella magneettikuvantamisella. Leikkaushoitoa suunniteltaessa kielellisiä alueita hallitseva aivopuolisko voidaan erottaa myös Wada-testin avulla. Sarjoittaista nTMS menetelmää hyödyntäviä kielellisten alueiden paikannusprotokollia on kehitetty, mutta niissä stimulaation aiheuttamia muutoksia potilaan suoriutumiseen annetusta tehtävästä on tyypillisesti voitu analysoida vain videotallenteita katsomalla. Erityisesti saatujen puhevasteiden toistettavaan ja objektiiviseen luokitteluun ja analyysiin on ollut tarjolla vain vähän menetelmiä. Analyysin helpottamiseksi kehitin kiihtyvyysanturisignaaliin perustuvan yksilöllisesti optimoidun puoliautomaattisen analysointirutiinin puhevasteiden viive-erojen määritykseen. Tulosten mukaan analysointirutiinin suorituskyky puhevasteiden viiveiden tunnistuksessa oli hyvä (sensitiivisyys 96 % ja spesifisyys 71 % verrattuna manuaaliseen analyysiin videolta ja suoraan signaalista). Väitöskirjassa esitettyjen tulosten perusteella voidaan todeta nTMS-menetelmän olevan käyttökelpoinen ja luotettava tutkimusmenetelmä vaikeaa epilepsiaa sairastavien potilaiden leikkausta edeltävään toiminnallisten alueiden kartoitukseen. nTMS-menetelmällä voidaan saada myös lisätietoa poikkeavan herkästi ärtyvistä aivoalueista

Modern Developments in Transcranial Magnetic Stimulation (TMS) – Applications and Perspectives in Clinical Neuroscience

Transcranial magnetic stimulation (TMS) is being increasingly used in neuroscience and clinics. Modern advances include but are not limited to the combination of TMS with precise neuronavigation as well as the integration of TMS into a multimodal environment, e.g., by guiding the TMS application using complementary techniques such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), diffusion tensor imaging (DTI), or magnetoencephalography (MEG). Furthermore, the impact of stimulation can be identified and characterized by such multimodal approaches, helping to shed light on the basic neurophysiology and TMS effects in the human brain. Against this background, the aim of this Special Issue was to explore advancements in the field of TMS considering both investigations in healthy subjects as well as patients

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

Review : Deep learning in electron microscopy

Deep learning is transforming most areas of science and technology, including electron microscopy. This review paper offers a practical perspective aimed at developers with limited familiarity. For context, we review popular applications of deep learning in electron microscopy. Following, we discuss hardware and software needed to get started with deep learning and interface with electron microscopes. We then review neural network components, popular architectures, and their optimization. Finally, we discuss future directions of deep learning in electron microscopy

Cybersecurity and the Digital Health: An Investigation on the State of the Art and the Position of the Actors

Cybercrime is increasingly exposing the health domain to growing risk. The push towards a strong connection of citizens to health services, through digitalization, has undisputed advantages. Digital health allows remote care, the use of medical devices with a high mechatronic and IT content with strong automation, and a large interconnection of hospital networks with an increasingly effective exchange of data. However, all this requires a great cybersecurity commitment—a commitment that must start with scholars in research and then reach the stakeholders. New devices and technological solutions are increasingly breaking into healthcare, and are able to change the processes of interaction in the health domain. This requires cybersecurity to become a vital part of patient safety through changes in human behaviour, technology, and processes, as part of a complete solution. All professionals involved in cybersecurity in the health domain were invited to contribute with their experiences. This book contains contributions from various experts and different fields. Aspects of cybersecurity in healthcare relating to technological advance and emerging risks were addressed. The new boundaries of this field and the impact of COVID-19 on some sectors, such as mhealth, have also been addressed. We dedicate the book to all those with different roles involved in cybersecurity in the health domain