Altered autonomic function in individuals at clinical high risk for psychosis

Introduction: Alterations in autonomic functioning in individuals diagnosed with schizophrenia are well-documented. Yet, it is currently unclear whether these dysfunctions extend into the clinical high-risk state. Thus, we investigated resting heart rate (RHR) and heart rate variability (HRV) indices in individuals at clinical high-risk for psychosis (CHR-P). Methods: We recruited 117 CHR-P participants, 38 participants with affective disorders and substance abuse (CHR-N) as well as a group of 49 healthy controls. CHR-P status was assessed with the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Schizophrenia Proneness Instrument, Adult Version (SPI-A). We obtained 5 min, eyes-open resting-state MEG data, which was used for the extraction of cardiac field-related inter-beat-interval data and from which heart-rate and heart-rate variability measures were computed. Results: Compared to both CHR-N and healthy controls, CHR-P participants were characterized by an increased RHR, which was not explained by differences in psychopathological comorbidity and medication status. Increased RHR correlated with the presence of subthreshold psychotic symptoms and associated distress. No differences between groups were found for heart-rate variability measures, however. Furthermore, there was an association between motor-performance and psychophysiological measures. Conclusion: The current study provides evidence of alterations in autonomic functioning as disclosed by increased RHR in CHR-P participants. Future studies are needed to further evaluate this characteristic feature of CHR-P individuals and its potential predictive value for psychosis development

Artifact removal in magnetoencephalogram background activity with independent component analysis

The aim of this study was to assess whether independent component analysis (ICA) could be valuable to remove power line noise, cardiac, and ocular artifacts from magnetoencephalogram (MEG) background activity. The MEGs were recorded from 11 subjects with a 148-channel whole-head magnetometer. We used a statistical criterion to estimate the number of independent components. Then, a robust ICA algorithm decomposed the MEG epochs and several methods were applied to detect those artifacts. The whole process had been previously tested on synthetic data. We found that the line noise components could be easily detected by their frequency spectrum. In addition, the ocular artifacts could be identified by their frequency characteristics and scalp topography. Moreover, the cardiac artifact was better recognized by its skewness value than by its kurtosis one. Finally, the MEG signals were compared before and after artifact rejection to evaluate our method

Seuratun kappaleen poikkeuttaminen silmänräpäysten aikana: käyttäytymis- ja neuromagneettisia havaintoja

The visual world is perceived as continuous despite frequent interruptions of sensory data due to eyeblinks and rapid eye movements. To create the perception of constancy, the brain makes use of fill-in mechanisms. This study presents an experiment in which the location of an object during smooth pursuit tracking is altered during eyeblinks. The experiment investigates the effects of blink suppression and fill-in mechanisms to cloud the discrimination of these changes. We employed a motion-tracking task, which promotes the accurate evaluation of the object’s trajectory and thus can counteract the fill-in mechanisms. Six subjects took part in the experiment, during which they were asked to report any perceived anomalies in the trajectory. Eye movements were monitored with a video-based tracking and brain responses with simultaneous MEG recordings. Discrimination success was found to depend on the direction of the displacement, and was significantly modulated by prior knowledge of the triggered effect. Eye-movement data were congruent with previous findings and revealed a smooth transition from blink recovery to object locating. MEG recordings were analysed for condition-dependent evoked and induced responses; however, intersubject variability was too large for drawing clear conclusions regarding the brain basis of the fill-in mechanisms.Visuaalinen maailma koetaan jatkuvana, vaikka silmänräpäykset ja nopeat silmänliikkeet aiheuttavat keskeytyksiä sensoriseen tiedonkeruuseen. Luodakseen käsityksen pysyvyydestä, aivot käyttävät täyttömekanismeja. Tämä tutkimus esittelee kokeen, jossa kappaleen seurantaa hitailla seurantaliikkeillä häiritään muuttamalla sen sijaintia silmänräpäysten aikana. Tämä koe tutkii, kuinka silmänräpäysten aiheuttama suppressio ja täyttömekanismit sumentavat kykyä erotella näitä muutoksia. Käytimme liikeseurantatehtävää, joka vastaavasti edistää kappaleen liikeradan tarkkaa arviointia. Kuusi koehenkilöä osallistui kokeeseen, jonka aikana heitä pyydettiin ilmoittamaan kaikki havaitut poikkeamat kappaleen liikeradassa. Silmänliikkeitä tallennettiin videopohjaisella seurannalla, ja aivovasteita yhtäaikaisella MEG:llä. Erottelykyvyn todettiin riippuvan poikkeutuksen suunnasta, sekä merkittävästi a priori tiedosta poikkeutusten esiintymistavasta. Silmänliikedata oli yhtenevää aiempien tutkimusten kanssa, ja paljasti sujuvan siirtymisen silmänräpäyksistä palautumisesta kappaleen paikallistamiseen. MEG-tallenteet analysoitiin ehdollisten heräte- ja indusoitujen vasteiden löytämiseksi, mutta yksilölliset vaste-erot koehenkilöiden välillä olivat liian suuria selkeiden johtopäätösten tekemiseksi täyttömekanismien aivoperustasta

Design of Integrated Neural/Modular Stimulators

Ph.DDOCTOR OF PHILOSOPH

Magnétomètres à pompage optique à Hélium 4 : développement et preuve de concept en magnétocardiographie et en magnétoencéphalographie

Magnetocardiography (MCG) and magnetoencephalography (MEG) are non-invasive techniques consisting in measuring respectively cardiac and brain magnetic fields. Despite their performance, the sensors currently used need a cryogenic cooling system which engenders technical and financial constraints. New cryogenic-free sensors have recently emerged: the OPMs (Optically-Pumped Magnetometers). Among them, vector 4He magnetometers developed by CEA-LETI which work at room-temperature. This thesis is focused on the development of 4He magnetometers dedicated to MCG and MEG.After having optimized the key-parameters of a first non-miniaturized prototype, a sensitivity inferior to 100 fT/sqrt(Hz) has been obtained along two axes. In order to meet biomedical constraints, a miniaturization of the device has been processed. In parallel, preclinical tests were carried out which have enabled us to design a gradiometer mode, a new packaging, and a magnetically isolated system. A noise analysis revealed that laser and HF discharge were the main sources of disturbance, and lead us to consider improvements such as a new detection mode. Eventually, a sensor, with a 1cm-sided cell, and an intrinsic sensitivity of 350 fT/√Hz has been developed.Then, device has been successfully tested in the frame of the MCG application from a healthy subject, preceded by a simulation study with a phantom which enables us to demonstrate its operability within a clinical environment. Moreover, we have proved the reproducibility of the measurements and the possibility to detect the main features of the cardiac cycle within a 30 s recording time. A specific optimization of the optical part has enabled us to obtain a 210 fT/sqrt(Hz) sensitivity between 3 and 300 Hz, suitable for the MEG application. After having tested our device with a phantom, three MEG experiments were performed with a healthy subject: auditory evoked field, visual evoked field and spontaneous activities have been detected. The obtained results form the first clinical proof of concept of the device for MCG and MEG applications.La magnétocardiographie (MCG) et la magnétoencéphalographie (MEG) sont deux techniques d'imagerie non-invasives mesurant respectivement les champs magnétiques cardiaques et cérébraux. Les dispositifs actuels utilisent des capteurs supraconducteurs de haute performance mais nécessitant un dispositif de refroidissement cryogénique, engendrant de fortes contraintes tant techniques que financières. Les magnétomètres à pompage optique (OPM) tendent à constituer une réelle alternative. Parmi eux figurent ceux développés au CEA-LETI, basés sur l'utilisation de l'hélium 4. Cette thèse a pour objectif de développer des magnétomètres vectoriels à 4He (fonctionnant à température ambiante) dédiés aux applications MCG et MEG.Après une optimisation des paramètres-clés d'un prototype non-miniaturisé préexistant, une sensibilité inférieure à 100 fT/sqrt(Hz) a pu être obtenue suivant deux axes. Afin de respecter les besoins spécifiques de la MCG et de la MEG une étape de miniaturisation a dû être menée et une architecture gradient-métrique a été mise en place. Parallèlement, des tests précliniques menés à Clinatec nous ont permis de concevoir un nouveau conditionnement du prototype, ainsi qu'un système réduisant les perturbations magnétiques. Une analyse des principales sources de bruit a révélé que les deux principaux contributeurs au bruit sont le laser et le système de décharge HF. Nous avons ainsi envisagé plusieurs pistes d'amélioration du niveau de bruit dont une nouvelle technique de détection. Le prototype issu de ces travaux comporte une pièce élémentaire (la cellule) d'un centimètre de côté, et présente une sensibilité intrinsèque de 350 fT/sqrt(Hz).Le dispositif a ensuite été testé avec succès dans le cadre de mesures MCG sur un sujet sain, précédées de tests sur fantôme ayant permis de prouver l'opérabilité de nos capteurs dans un environnement clinique. Par ailleurs, la reproductibilité des résultats ainsi que la possibilité de réduire à 30 s le temps d'acquisition des données ont pu être démontrées. Une optimisation spécifique de la partie optique du prototype a permis d'obtenir une sensibilité de l'ordre de 210 fT/sqrt(Hz) entre 3 et 300 Hz, compatible avec l'application MEG. Après des tests menés avec succès sur fantôme, trois séries d'essais ont été réalisées sur un sujet sain. Nous avons pu ainsi détecter des potentiels évoqués auditifs, visuels ainsi qu'une modulation de l'activité cérébrale spontanée sous l'effet de l'ouverture des paupières. L'ensemble des résultats obtenus constitue les premières preuves de concept cliniques du dispositif en MCG et MEG

Magnetoencephalography

This is a practical book on MEG that covers a wide range of topics. The book begins with a series of reviews on the use of MEG for clinical applications, the study of cognitive functions in various diseases, and one chapter focusing specifically on studies of memory with MEG. There are sections with chapters that describe source localization issues, the use of beamformers and dipole source methods, as well as phase-based analyses, and a step-by-step guide to using dipoles for epilepsy spike analyses. The book ends with a section describing new innovations in MEG systems, namely an on-line real-time MEG data acquisition system, novel applications for MEG research, and a proposal for a helium re-circulation system. With such breadth of topics, there will be a chapter that is of interest to every MEG researcher or clinician