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Investigating the relationship between task-related hemodynamic responses and cortical excitability is challenging because it requires simultaneous measurement of hemodynamic responses while applying noninvasive brain stimulation. Moreover, cortical excitability and task-related hemodynamic responses are both associated with inter-/intra-subject variability. To reliably assess such a relationship, we applied hierarchical Bayesian modeling. This study involved 16 healthy subjects who underwent simultaneous Paired Associative Stimulation (PAS10, PAS25, Sham) while monitoring brain activity using functional Near-Infrared Spectroscopy (fNIRS), targeting the primary motor cortex (M1). Cortical excitability was measured by Motor Evoked Potentials (MEPs), and the motor task-related hemodynamic responses were measured using fNIRS 3D reconstructions. We constructed three models to investigate: (1) PAS effects on the M1 excitability, (2) PAS effects on fNIRS hemodynamic responses to a finger tapping task, and (3) the correlation between PAS effects on M1 excitability and PAS effects on task-related hemodynamic responses. Significant increase in cortical excitability was found following PAS25, whereas a small reduction of the cortical excitability was shown after PAS10 and a subtle increase occurred after sham. Both HbO and HbR absolute amplitudes increased after PAS25 and decreased after PAS10. The probability of the positive correlation between modulation of cortical excitability and hemodynamic activity was 0.77 for HbO and 0.79 for HbR. We demonstrated that PAS stimulation modulates task-related cortical hemodynamic responses in addition to M1 excitability. Moreover, the positive correlation between PAS modulations of excitability and hemodynamics brought insight into understanding the fundamental properties of cortical function and cortical excitability., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

In the present study, we proposed and evaluated a workflow of personalized near infra-red optical tomography (NIROT) using functional near-infrared spectroscopy (fNIRS) for spatiotemporal imaging of cortical hemodynamic fluctuations. The proposed workflow from fNIRS data acquisition to local 3D reconstruction consists of: (a) the personalized optimal montage maximizing fNIRS channel sensitivity to a predefined targeted brain region; (b) the optimized fNIRS data acquisition involving installation of optodes and digitalization of their positions using a neuronavigation system; and (c) the 3D local reconstruction using maximum entropy on the mean (MEM) to accurately estimate the location and spatial extent of fNIRS hemodynamic fluctuations along the cortical surface. The workflow was evaluated on finger-tapping fNIRS data acquired from 10 healthy subjects for whom we estimated the reconstructed NIROT spatiotemporal images and compared with functional magnetic resonance imaging (fMRI) results from the same individuals. Using the fMRI activation maps as our reference, we quantitatively compared the performance of two NIROT approaches, the MEM framework and the conventional minimum norm estimation (MNE) method. Quantitative comparisons were performed at both single subject and group-level. Overall, our results suggested that MEM provided better spatial accuracy than MNE, while both methods offered similar temporal accuracy when reconstructing oxygenated (HbO) and deoxygenated hemoglobin (HbR) concentration changes evoked by finger-tapping. Our proposed complete workflow was made available in the brainstorm fNIRS processing plugin-NIRSTORM, thus providing the opportunity for other researchers to further apply it to other tasks and on larger populations., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Interactions between interictal epileptiform discharges (IEDs) and distant cortical regions subserve potential effects on cognition of patients with focal epilepsy. We hypothesize that "healthy" brain areas at a distance from the epileptic focus may respond to the interference of IEDs by generating inhibitory alpha and beta oscillations. We predict that more prominent alpha-beta oscillations can be found in patients with less impaired neurocognitive profile. We performed a source imaging magnetoencephalography study, including 41 focal epilepsy patients: 21 with frontal lobe epilepsy (FLE) and 20 with mesial temporal lobe epilepsy. We investigated the effect of anterior (i.e., frontal and temporal) IEDs on the oscillatory pattern over posterior head regions. We compared cortical oscillations (5-80 Hz) temporally linked to 3,749 IEDs (1,945 frontal and 1,803 temporal) versus an equal number of IED-free segments. We correlated results from IED triggered oscillations to global neurocognitive performance. Only frontal IEDs triggered alpha-beta oscillations over posterior head regions. IEDs with higher amplitude triggered alpha-beta oscillations of higher magnitude. The intensity of posterior head region alpha-beta oscillations significantly correlated with a better neuropsychological profile. Our study demonstrated that cerebral cortex protects itself from IEDs with generation of inhibitory alpha-beta oscillations at distant cortical regions. The association of more prominent oscillations with a better cognitive status suggests that this mechanism might play a role in determining the cognitive resilience in patients with FLE., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Source localization of interictal epileptiform discharges (IEDs) is clinically useful in the presurgical workup of epilepsy patients. We aimed to compare the performance of four different distributed magnetic source imaging (dMSI) approaches: Minimum norm estimate (MNE), dynamic statistical parametric mapping (dSPM), standardized low-resolution electromagnetic tomography (sLORETA), and coherent maximum entropy on the mean (cMEM). We also evaluated whether a simple average of maps obtained from multiple inverse solutions (Ave) can improve localization accuracy. We analyzed dMSI of 206 IEDs derived from magnetoencephalography recordings in 28 focal epilepsy patients who had a well-defined focus determined through intracranial EEG (iEEG), epileptogenic MRI lesions or surgical resection. dMSI accuracy and spatial properties were quantitatively estimated as: (a) distance from the epilepsy focus, (b) reproducibility, (c) spatial dispersion (SD), (d) map extension, and (e) effect of thresholding on map properties. Clinical performance was excellent for all methods (median distance from the focus MNE = 2.4 mm; sLORETA = 3.5 mm; cMEM = 3.5 mm; dSPM = 6.8 mm, Ave = 0 mm). Ave showed the lowest distance between the map maximum and epilepsy focus (Dmin lower than cMEM, MNE, and dSPM, p = .021, p = .008, p < .001, respectively). cMEM showed the best spatial features, with lowest SD outside the focus (SD lower than all other methods, p < .001 consistently) and high contrast between the generator and surrounding regions. The average map Ave provided the best localization accuracy, whereas cMEM exhibited the lowest amount of spurious distant activity. dMSI techniques have the potential to significantly improve identification of iEEG targets and to guide surgical planning, especially when multiple methods are combined., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique able to induce plasticity phenomena. Although tDCS application has been spreading over a variety of neuroscience domains, the mechanisms by which the stimulation acts are largely unknown. We investigated tDCS effects on cortical gamma synchrony, which is a crucial player in cortical function. We performed a randomized, sham-controlled, double-blind study on healthy subjects, combining tDCS and magnetoencephalography. By driving brain activity via 40 Hz auditory stimulation during magnetoencephalography, we experimentally tuned cortical gamma synchrony and measured it before and after bilateral tDCS of the primary sensory-motor hand regions (anode left, cathode right). We demonstrated that the stimulation induces a remarkable decrease of gamma synchrony (13 out of 15 subjects), as measured by gamma phase at 40 Hz. tDCS has strong remote effects, as the cortical region mostly affected was located far away from the stimulation site and covered a large area of the right centro-temporal cortex. No significant differences between stimulations were found for baseline gamma synchrony, as well as early transient auditory responses. This suggests a specific tDCS effect on externally driven gamma synchronization. This study sheds new light on the effect of tDCS on cortical function showing that the net effect of the stimulation on cortical gamma synchronization is an inhibition., (© 2019 Wiley Periodicals, Inc.)

Fusion of electroencephalography (EEG) and magnetoencephalography (MEG) data using maximum entropy on the mean method (MEM-fusion) takes advantage of the complementarities between EEG and MEG to improve localization accuracy. Simulation studies demonstrated MEM-fusion to be robust especially in noisy conditions such as single spike source localizations (SSSL). Our objective was to assess the reliability of SSSL using MEM-fusion on clinical data. We proposed to cluster SSSL results to find the most reliable and consistent source map from the reconstructed sources, the so-called consensus map. Thirty-four types of interictal epileptic discharges (IEDs) were analyzed from 26 patients with well-defined epileptogenic focus. SSSLs were performed on EEG, MEG, and fusion data and consensus maps were estimated using hierarchical clustering. Qualitative (spike-to-spike reproducibility rate, SSR) and quantitative (localization error and spatial dispersion) assessments were performed using the epileptogenic focus as clinical reference. Fusion SSSL provided significantly better results than EEG or MEG alone. Fusion found at least one cluster concordant with the clinical reference in all cases. This concordant cluster was always the one involving the highest number of spikes. Fusion yielded highest reproducibility (SSR EEG = 55%, MEG = 71%, fusion = 90%) and lowest localization error. Also, using only few channels from either modality (21EEG + 272MEG or 54EEG + 25MEG) was sufficient to reach accurate fusion. MEM-fusion with consensus map approach provides an objective way of finding the most reliable and concordant generators of IEDs. We, therefore, suggest the pertinence of SSSL using MEM-fusion as a valuable clinical tool for presurgical evaluation of epilepsy., (© 2017 Wiley Periodicals, Inc.)

Objective: Source localization of interictal epileptic discharges (IEDs) is clinically useful in the presurgical workup of epilepsy patients. It is usually obtained by equivalent current dipole (ECD) which localizes a point source and is the only inverse solution approved by clinical guidelines. In contrast, magnetic source imaging using distributed methods (dMSI) provides maps of the location and the extent of the generators, but its yield has not been clinically validated. We systematically compared ECD versus dMSI performed using coherent Maximum Entropy on the Mean (cMEM), a method sensitive to the spatial extent of the generators., Methods: 340 source localizations of IEDs derived from 49 focal epilepsy patients with foci well-defined through intracranial EEG, MRI lesions, and surgery were analyzed. The comparison was based on the assessment of the sublobar concordance with the focus and of the distance between the source and the focus., Results: dMSI sublobar concordance was significantly higher than ECD (81% vs 69%, P < 0.001), especially for extratemporal lobe sources (dMSI = 84%; ECD = 67%, P < 0.001) and for seizure free patients (dMSI = 83%; ECD = 70%, P < 0.001). The median distance from the focus was 4.88 mm for ECD and 3.44 mm for dMSI (P < 0.001). ECD dipoles were often wrongly localized in deep brain regions., Conclusions: dMSI using cMEM exhibited better accuracy. dMSI also offered the advantage of recovering more realistic maps of the generator, which could be exploited for neuronavigation aimed at targeting invasive EEG and surgical resection. Therefore, dMSI may be preferred to ECD in clinical practice. Hum Brain Mapp 39:218-231, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Introduction: Surgical treatment of drug-resistant epilepsy relies on the identification of the seizure onset zone (SOZ) and often requires intracranial EEG (iEEG). We have developed a new approach for non-invasive magnetic and electric source imaging of the SOZ (MSI-SOZ and ESI-SOZ) from ictal magnetoencephalography (MEG) and EEG recordings, using wavelet-based Maximum Entropy on the Mean (wMEM) method. We compared the performance of MSI-SOZ and ESI-SOZ with interictal spike source localization (MSI-spikes and ESI-spikes) and clinical localization of the SOZ (i.e., based on iEEG or lesion topography, denoted as clinical-SOZ)., Methods: A total of 46 MEG or EEG seizures from 13 patients were analyzed. wMEM was applied around seizure onset, centered on the frequency band showing the strongest power change. Principal component analysis applied to spatiotemporal reconstructed wMEM sources (0.4-1 s around seizure onset) identified the main spatial pattern of ictal oscillations. Qualitative sublobar concordance and quantitative measures of distance and spatial overlaps were estimated to compare MSI/ESI-SOZ with MSI/ESI-Spikes and clinical-SOZ., Results: MSI/ESI-SOZ were concordant with clinical-SOZ in 81% of seizures (MSI 90%, ESI 64%). MSI-SOZ was more accurate and identified sources closer to the clinical-SOZ (P = 0.012) and to MSI-Spikes (P = 0.040) as compared with ESI-SOZ. MSI/ESI-SOZ and MSI/ESI-Spikes did not differ in terms of concordance and distance from the clinical-SOZ., Conclusions: wMEM allows non-invasive localization of the SOZ from ictal MEG and EEG. MSI-SOZ performs better than ESI-SOZ. MSI/ESI-SOZ can provide important additional information to MSI/ESI-Spikes during presurgical evaluation. Hum Brain Mapp 37:2528-2546, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Brain effective connectivity can be tracked by cerebral recruitments evoked by transcranial magnetic stimulation (TMS), as measured by simultaneous electroencephalography (TMS-EEG). When TMS is targeting the primary motor area, motor evoked potentials (MEPs) can be collected from the "target" muscles. The aim of this study was to measure whether or not effective brain connectivity changes with the excitability level of the corticospinal motor pathway (CSMP) as parameterized by MEP amplitude. After averaging two subgroups of EEG-evoked responses corresponding to high and low MEP amplitudes, we calculated the individual differences between them and submitted the grand average to sLORETA algorithm obtaining localized regions of interest (RoIs). Statistical differences of RoI recruitment strength between low and high CSMP excitation was assessed in single subjects. Preceding the feedback arrival, neural recruitment for stronger CSMP activation were weaker at 6-10 ms of homotopic sensorimotor areas BA3/4/5 of the right nonstimulated hemisphere (trend), weaker at 18-25 ms of left parietal BA2/3/40, and stronger at 26-32 ms of bilateral frontal motor areas BA6/8. The proposed method enables the tracking of brain network connectivity during stimulation of one node by measuring the strength of the connected recruited node activations. Spontaneous increases of the excitation of the node originating the transmission within the hand control network gave rise to dynamic recruitment patterns with opposite behaviors, weaker in homotopic and parietal circuits, stronger in frontal ones. The effective connectivity within bilateral circuits orchestrating hand control appeared dynamically modulated in time even in resting state as probed by TMS., (Copyright © 2013 Wiley Periodicals, Inc.)