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WIRSICH Jonathan

PhD Student

jonathan.wirsich@univ-amu.fr
tel : +33 4 91 38 84 68
Key Words
- EEG-fMRI
- computational neurosciences
- data fusion
- connectivity

Current Research Interest and projects

Computational simultaneous EEG-fMRI data fusion models in human brain pathologies

2017

Journal Article

  • RIDLEY B., MARCHI A., WIRSICH J., SOULIER E., CONFORT-GOUNY S., SCHAD L., BARTOLOMEI F., RANJEVA J. - P., GUYE M., ZAARAOUI W. “Brain sodium MRI in human epilepsy: Disturbances of ionic homeostasis reflect the organization of pathological regions.”. NeuroImage [En ligne]. 7 June 2017. Vol. 157, p. 173-183. Disponible sur : < http://dx.doi.org/10.1016/j.neuroimage.2017.06.011 > (consulté le no date)
    Résumé : In light of technical advancements supporting exploration of MR signals other than (1)H, sodium ((23)Na) has received attention as a marker of ionic homeostasis and cell viability. Here, we evaluate for the first time the possibility that (23)Na-MRI is sensitive to pathological processes occurring in human epilepsy. A normative sample of 27 controls was used to normalize regions of interest (ROIs) from 1424 unique brain locales on quantitative (23)Na-MRI and high-resolution (1)H-MPRAGE images. ROIs were based on intracerebral electrodes in ten patients undergoing epileptic network mapping. The stereo-EEG gold standard was used to define regions as belonging to primarily epileptogenic, secondarily irritative and to non-involved regions. Estimates of total sodium concentration (TSC) on (23)Na-MRI and cerebrospinal fluid (CSF) on (1)H imaging were extracted for each patient ROI, and normalized against the same region in controls. ROIs with disproportionate CSF contributions (ZCSF≥1.96) were excluded. TSC levels were found to be elevated in patients relative to controls except in one patient, who suffered non-convulsive seizures during the scan, in whom we found reduced TSC levels. In the remaining patients, an ANOVA (F1100= 12.37, p<0.0001) revealed a highly significant effect of clinically-defined zones (F1100= 11.13, p<0.0001), with higher normalized TSC in the epileptogenic zone relative to both secondarily irritative (F1100= 11, p=0.0009) and non-involved regions (F1100= 17.8, p<0.0001). We provide the first non-invasive, in vivo evidence of a chronic TSC elevation alongside ZCSF levels within the normative range, associated with the epileptogenic region even during the interictal period in human epilepsy, and the possibility of reduced TSC levels due to seizure. In line with modified homeostatic mechanisms in epilepsy - including altered mechanisms underlying ionic gating, clearance and exchange - we provide the first indication of (23)Na-MRI as an assay of altered sodium concentrations occurring in epilepsy associated with the organization of clinically relevant divisions of pathological cortex.
    Mots-clés : Cortical localisation, crmbm, epilepsy, Epilepsy surgery, Intracranial EEG, Ionic imaging, snc, Sodium MRI.

  • RIDLEY B., WIRSICH J., BETTUS G., RODIONOV R., MURTA T., CHAUDHARY U., CARMICHAEL D., THORNTON R., VULLIEMOZ S., MCEVOY A., WENDLING F., BARTOLOMEI F., RANJEVA J. - P., LEMIEUX L., GUYE M. “Simultaneous Intracranial EEG-fMRI Shows Inter-Modality Correlation in Time-Resolved Connectivity Within Normal Areas but Not Within Epileptic Regions.”. Brain Topography [En ligne]. 13 February 2017. Disponible sur : < http://dx.doi.org/10.1007/s10548-017-0551-5 > (consulté le no date)
    Résumé : For the first time in research in humans, we used simultaneous icEEG-fMRI to examine the link between connectivity in haemodynamic signals during the resting-state (rs) and connectivity derived from electrophysiological activity in terms of the inter-modal connectivity correlation (IMCC). We quantified IMCC in nine patients with drug-resistant epilepsy (i) within brain networks in 'healthy' non-involved cortical zones (NIZ) and (ii) within brain networks involved in generating seizures and interictal spikes (IZ1) or solely spikes (IZ2). Functional connectivity (h (2) ) estimates for 10 min of resting-state data were obtained between each pair of electrodes within each clinical zone for both icEEG and fMRI. A sliding window approach allowed us to quantify the variability over time of h (2) (vh (2)) as an indicator of connectivity dynamics. We observe significant positive IMCC for h (2) and vh (2), for multiple bands in the NIZ only, with the strongest effect in the lower icEEG frequencies. Similarly, intra-modal h (2) and vh (2) were found to be differently modified as a function of different epileptic processes: compared to NIZ, [Formula: see text] was higher in IZ1, but lower in IZ2, while [Formula: see text] showed the inverse pattern. This corroborates previous observations of inter-modal connectivity discrepancies in pathological cortices, while providing the first direct invasive and simultaneous comparison in humans. We also studied time-resolved FC variability multimodally for the first time, finding that IZ1 shows both elevated internal [Formula: see text] and less rich dynamical variability, suggesting that its chronic role in epileptogenesis may be linked to greater homogeneity in self-sustaining pathological oscillatory states.
    Mots-clés : connectivity, crmbm, Dynamic connectivity, Focal epilepsy, Multimodal imaging, Resting-state, snc.

2016

Journal Article

  • BOUTIÈRE C., REY C., ZAARAOUI W., LE TROTER A., RICO A., CRESPY L., ACHARD S., REUTER F., PARIOLLAUD F., WIRSICH J., ASQUINAZI P., CONFORT-GOUNY S., SOULIER E., GUYE M., PELLETIER J., RANJEVA J. - P., AUDOIN B. “Improvement of spasticity following intermittent theta burst stimulation in multiple sclerosis is associated with modulation of resting-state functional connectivity of the primary motor cortices.”. Multiple Sclerosis (Houndmills, Basingstoke, England) [En ligne]. 1 August 2016. Disponible sur : < http://dx.doi.org/10.1177/1352458516661640 > (consulté le no date)
    Résumé : BACKGROUND: Intermittent theta burst stimulation (iTBS) of the primary motor cortex improves transiently lower limbs spasticity in multiple sclerosis (MS). However, the cerebral mechanisms underlying this effect have never been investigated. OBJECTIVE: To assess whether modulation of spasticity induced by iTBS is underlined by functional reorganization of the primary motor cortices. METHODS: A total of 17 patients with MS suffering from lower limbs spasticity were randomized to receive real iTBS or sham iTBS during the first half of a 5-week indoor rehabilitation programme. Spasticity was assessed using the Modified Ashworth Scale and the Visual Analogue Scale at baseline, after the stimulation session and at the end of the rehabilitation programme. Resting-state functional magnetic resonance imaging (fMRI) was performed at the three time points, and brain functional networks topology was analysed using graph-theoretical approach. RESULTS: At the end of stimulation, improvement of spasticity was greater in real iTBS group than in sham iTBS group (p = 0.026). iTBS had a significant effect on the balance of the connectivity degree between the stimulated and the homologous primary motor cortex (p = 0.005). Changes in inter-hemispheric balance were correlated with improvement of spasticity (rho = 0.56, p = 0.015). CONCLUSION: This longitudinal resting-state fMRI study evidences that functional reorganization of the primary motor cortices may underlie the effect of iTBS on spasticity in MS.
    Mots-clés : connectivity, crmbm, intermittent theta burst stimulation, Multiple Sclerosis, primary motor cortex, resting state fMRI, snc, spasticity.

  • RIDLEY B., BELTRAMONE M., WIRSICH J., LE TROTER A., TRAMONI E., AUBERT S., ACHARD S., RANJEVA J. - P., GUYE M., FELICIAN O. “Alien Hand, Restless Brain: Salience Network and Interhemispheric Connectivity Disruption Parallel Emergence and Extinction of Diagonistic Dyspraxia.”. Frontiers in Human Neuroscience [En ligne]. 2016. Vol. 10, p. 307. Disponible sur : < http://dx.doi.org/10.3389/fnhum.2016.00307 > (consulté le no date)
    Résumé : Diagonistic dyspraxia (DD) is by far the most spectacular manifestation reported by sufferers of acute corpus callosum (CC) injury (so-called "split-brain"). In this form of alien hand syndrome, one hand acts at cross purposes with the other "against the patient's will". Although recent models view DD as a disorder of motor control, there is still little information regarding its neural underpinnings, due to widespread connectivity changes produced by CC insult, and the obstacle that non-volitional movements represent for task-based functional neuroimaging studies. Here, we studied patient AM, the first report of DD in patient with complete developmental CC agenesis. This unique case also offers the opportunity to study the resting-state connectomics of DD in the absence of diffuse changes subsequent to CC injury or surgery. AM developed DD following status epilepticus (SE) which resolved over a 2-year period. Whole brain functional connectivity (FC) was compared (Crawford-Howell [CH]) to 16 controls during the period of acute DD symptoms (Time 1) and after remission (Time 2). Whole brain graph theoretical models were also constructed and topological efficiency examined. At Time 1, disrupted FC was observed in inter-hemispheric and intra-hemispheric right edges, involving frontal superior and midline structures. Graph analysis indicated disruption of the efficiency of salience and right frontoparietal (FP) networks. At Time 2, after remission of diagnostic dyspraxia symptoms, FC and salience network changes had resolved. In sum, longitudinal analysis of connectivity in AM indicates that DD behaviors could result from disruption of systems that support the experience and control of volitional movements and the ability to generate appropriate behavioral responses to salient stimuli. This also raises the possibility that changes to large-scale functional architecture revealed by resting-state functional magnetic resonance imaging (fMRI) (rs-fMRI) may provide relevant information on the evolution of behavioral syndromes in addition to that provided by structural and task-based functional imaging.
    Mots-clés : alien hand, callosal agenesis, crmbm, disconnection syndrome, epilepsy, Functional connectivity, graph theory, Resting-state, snc.


  • WIRSICH J., PERRY A., RIDLEY B., PROIX T., GOLOS M., BÉNAR C., RANJEVA J. - P., BARTOLOMEI F., BREAKSPEAR M., JIRSA V., GUYE M. “Whole-brain analytic measures of network communication reveal increased structure-function correlation in right temporal lobe epilepsy.”. NeuroImage: Clinical [En ligne]. 2016. Vol. 11, p. 707-718. Disponible sur : < http://dx.doi.org/10.1016/j.nicl.2016.05.010 > (consulté le 7 June 2016)
    Résumé : The in vivo structure-function relationship is key to understanding brain network reorganization due to pathologies. This relationship is likely to be particularly complex in brain network diseases such as temporal lobe epilepsy, in which disturbed large-scale systems are involved in both transient electrical events and long-lasting functional and structural impairments. Herein, we estimated this relationship by analyzing the correlation between structural connectivity and functional connectivity in terms of analytical network communication parameters. As such, we targeted the gradual topological structure-function reorganization caused by the pathology not only at the whole brain scale but also both in core and peripheral regions of the brain. We acquired diffusion (dMRI) and resting-state fMRI (rsfMRI) data in seven right-lateralized TLE (rTLE) patients and fourteen healthy controls and analyzed the structure-function relationship by using analytical network communication metrics derived from the structural connectome. In rTLE patients, we found a widespread hypercorrelated functional network. Network communication analysis revealed greater unspecific branching of the shortest path (search information) in the structural connectome and a higher global correlation between the structural and functional connectivity for the patient group. We also found evidence for a preserved structural rich-club in the patient group. In sum, global augmentation of structure-function correlation might be linked to a smaller functional repertoire in rTLE patients, while sparing the central core of the brain which may represent a pathway that facilitates the spread of seizures.
    Mots-clés : crmbm, Functional connectivity, Network based statistics, Network communication, rich club, snc, structural connectivity, Temporal lobe epilepsy.

2015

Journal Article

  • FAGET-AGIUS C., CATHERINE F. - A., BOYER L., WIRSICH J., JONATHAN W., RANJEVA J. - P., JEAN-PHILIPPE R., RICHIERI R., RAPHAELLE R., SOULIER E., ELISABETH S., CONFORT-GOUNY S., SYLVIANE C. - G., AUQUIER P., PASCAL A., GUYE M., MAXIME G., LANÇON C., CHRISTOPHE L. “Neural substrate of quality of life in patients with schizophrenia: a magnetisation transfer imaging study.”. Scientific Reports [En ligne]. 3 December 2015. Vol. 5, p. 17650. Disponible sur : < http://dx.doi.org/10.1038/srep17650 > (consulté le no date)
    Résumé : The aim of this study was to investigate the neural substrate underlying quality of life (QoL) and to demonstrate the microstructural abnormalities associated with impaired QoL in a large sample of patients with schizophrenia, using magnetisation transfer imaging. A total of 81 right-handed men with a diagnosis of schizophrenia and 25 age- and sex-similar healthy controls were included and underwent a 3T MRI with magnetization transfer ratio (MTR) to detect microstructural abnormalities. Compared with healthy controls, patients with schizophrenia had grey matter (GM) decreased MTR values in the temporal lobe (BA21, BA37 and BA38), the bilateral insula, the occipital lobe (BA17, BA18 and BA19) and the cerebellum. Patients with impaired QoL had lower GM MTR values relative to patients with preserved QoL in the bilateral temporal pole (BA38), the bilateral insula, the secondary visual cortex (BA18), the vermis and the cerebellum. Significant correlations between MTR values and QoL scores (p < 0.005) were observed in the GM of patients in the right temporal pole (BA38), the bilateral insula, the vermis and the right cerebellum. Our study shows that QoL impairment in patients with schizophrenia is related to the microstructural changes in an extensive network, suggesting that QoL is a bio-psychosocial marker.
    Mots-clés : Adolescent, Adult, Brain, Cerebral Cortex, crmbm, Gray matter, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neurons, Quality of Life, Radiography, Schizophrenia, snc, Surveys and Questionnaires, Temporal Lobe.

  • RIDLEY B. G. Y., ROUSSEAU C., WIRSICH J., LE TROTER A., SOULIER E., CONFORT-GOUNY S., BARTOLOMEI F., RANJEVA J. - P., ACHARD S., GUYE M. “Nodal approach reveals differential impact of lateralized focal epilepsies on hub reorganization.”. NeuroImage [En ligne]. September 2015. Vol. 118, p. 39-48. Disponible sur : < http://dx.doi.org/10.1016/j.neuroimage.2015.05.096 > (consulté le no date)
    Résumé : The impact of the hemisphere affected by impairment in models of network disease is not fully understood. Among such models, focal epilepsies are characterised by recurrent seizures generated in epileptogenic areas also responsible for wider network dysfunction between seizures. Previous work focusing on functional connectivity within circumscribed networks suggests a divergence of network integrity and compensatory capacity between epilepsies as a function of the laterality of seizure onset. We evaluated the ability of complex network theory to reveal changes in focal epilepsy in global and nodal parameters using graph theoretical analysis of functional connectivity data obtained with resting-state fMRI. Graphs of functional connectivity networks were derived from 19 right and 13 left focal epilepsy patients and 15 controls. Topological metrics (degree, local efficiency, global efficiency and modularity) were computed for a whole-brain, atlas-defined network. We also calculated a hub disruption index for each graph metric, measuring the capacity of the brain network to demonstrate increased connectivity in some nodes for decreased connectivity in others. Our data demonstrate that the patient group as a whole is characterised by network-wide pattern of reorganization, even while global parameters fail to distinguish between groups. Furthermore, multiple metrics indicate that epilepsies with differently lateralized epileptic networks are asymmetric in their burden on functional brain networks; with left epilepsy patients being characterised by reduced efficiency and modularity, while in right epilepsy patients we provide the first evidence that functional brain networks are characterised by enhanced connectivity and efficiency at some nodes whereas reduced in others.
    Mots-clés : crmbm, epilepsy, Functional connectivity, graph theory, Hemispheric asymmetry, Network modelling, Resting-state, snc.

2014

Journal Article


  • WIRSICH J., BÉNAR C., RANJEVA J. - P., DESCOINS M., SOULIER E., LE TROTER A., CONFORT-GOUNY S., LIÉGEOIS-CHAUVEL C., GUYE M. “Single-trial EEG-informed fMRI reveals spatial dependency of BOLD signal on early and late IC-ERP amplitudes during face recognition.”. NeuroImage [En ligne]. 15 October 2014. Vol. 100, p. 325-336. Disponible sur : < http://dx.doi.org/10.1016/j.neuroimage.2014.05.075 > (consulté le 4 August 2014)
    Résumé : Simultaneous EEG-fMRI has opened up new avenues for improving the spatio-temporal resolution of functional brain studies. However, this method usually suffers from poor EEG quality, especially for evoked potentials (ERPs), due to specific artifacts. As such, the use of EEG-informed fMRI analysis in the context of cognitive studies has particularly focused on optimizing narrow ERP time windows of interest, which ignores the rich diverse temporal information of the EEG signal. Here, we propose to use simultaneous EEG-fMRI to investigate the neural cascade occurring during face recognition in 14 healthy volunteers by using the successive ERP peaks recorded during the cognitive part of this process. N170, N400 and P600 peaks, commonly associated with face recognition, were successfully and reproducibly identified for each trial and each subject by using a group independent component analysis (ICA). For the first time we use this group ICA to extract several independent components (IC) corresponding to the sequence of activation and used single-trial peaks as modulation parameters in a general linear model (GLM) of fMRI data. We obtained an occipital–temporal–frontal stream of BOLD signal modulation, in accordance with the three successive IC-ERPs providing an unprecedented spatio-temporal characterization of the whole cognitive process as defined by BOLD signal modulation. By using this approach, the pattern of EEG-informed BOLD modulation provided improved characterization of the network involved than the fMRI-only analysis or the source reconstruction of the three ERPs; the latter techniques showing only two regions in common localized in the occipital lobe.
    Mots-clés : crmbm, Evoked Potentials, Face recognition, ICA, Simultaneous EEG-fMRI, Ventral visual pathway.
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