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Alzheimer’s disease (AD) is a progressive neuropsychiatric disease affecting many elderly people and is characterized by progressive cognitive impairment of memory, visuospatial, and executive functions. As the elderly population is growing, the number of AD patients is increasing considerably. There is currently growing interest in determining AD’s cognitive dysfunction markers. We used exact low-resolution-brain-electromagnetic-tomography independent-component-analysis (eLORETA-ICA) to assess activities of five electroencephalography resting-state-networks (EEG-RSNs) in 90 drug-free AD patients and 11 drug-free patients with mild-cognitive-impairment due to AD (ADMCI). Compared to 147 healthy subjects, the AD/ADMCI patients showed significantly decreased activities in the memory network and occipital visual network, where the age difference between the AD/ADMCI and healthy groups was corrected by linear regression analysis. Furthermore, the age-corrected EEG-RSN activities showed correlations with cognitive function test scores in AD/ADMCI. In particular, decreased memory network activity showed correlations with worse total cognitive scores for both Mini-Mental-State-Examination (MMSE) and Alzheimer’s Disease-Assessment-Scale-cognitive-component-Japanese version (ADAS-J cog) including worse sub-scores for orientation, registration, repetition, word recognition and ideational praxis. Our results indicate that AD affects specific EEG-RSNs and deteriorated network activity causes symptoms. Overall, eLORETA-ICA is a useful, non-invasive tool for assessing EEG-functional-network activities and provides better understanding of the neurophysiological mechanisms underlying the disease.

In 1999, the International Federation of Clinical Neurophysiology (IFCN) published "IFCN Guidelines for topographic and frequency analysis of EEGs and EPs" (Nuwer et al., 1999). Here a Workgroup of IFCN experts presents unanimous recommendations on the following procedures relevant for the topographic and frequency analysis of resting state EEGs (rsEEGs) in clinical research defined as neurophysiological experimental studies carried out in neurological and psychiatric patients: (1) recording of rsEEGs (environmental conditions and instructions to participants; montage of the EEG electrodes; recording settings); (2) digital storage of rsEEG and control data; (3) computerized visualization of rsEEGs and control data (identification of artifacts and neuropathological rsEEG waveforms); (4) extraction of "synchronization" features based on frequency analysis (band-pass filtering and computation of rsEEG amplitude/power density spectrum); (5) extraction of "connectivity" features based on frequency analysis (linear and nonlinear measures); (6) extraction of "topographic" features (topographic mapping; cortical source mapping; estimation of scalp current density and dura surface potential; cortical connectivity mapping), and (7) statistical analysis and neurophysiological interpretation of those rsEEG features. As core outcomes, the IFCN Workgroup endorsed the use of the most promising "synchronization" and "connectivity" features for clinical research, carefully considering the limitations discussed in this paper. The Workgroup also encourages more experimental (i.e. simulation studies) and clinical research within international initiatives (i.e., shared software platforms and databases) facing the open controversies about electrode montages and linear vs. nonlinear and electrode vs. source levels of those analyses. (C) 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.

To date, electroencephalogram (EEG) has been used in the diagnosis of epilepsy, dementia, and disturbance of consciousness via the inspection of EEG waves and identification of abnormal electrical discharges and slowing of basic waves. In addition, EEG power analysis combined with a source estimation method like exact-low-resolution-brain-electromagnetic-tomography (eLORETA), which calculates the power of cortical electrical activity from EEG data, has been widely used to investigate cortical electrical activity in neuropsychiatric diseases. However, the recently developed field of mathematics “information geometry” indicates that EEG has another dimension orthogonal to power dimension — that of normalized power variance (NPV). In addition, by introducing the idea of information geometry, a significantly faster convergent estimator of NPV was obtained. Research into this NPV coordinate has been limited thus far. In this study, we applied this NPV analysis of eLORETA to idiopathic normal pressure hydrocephalus (iNPH) patients prior to a cerebrospinal fluid (CSF) shunt operation, where traditional power analysis could not detect any difference associated with CSF shunt operation outcome. Our NPV analysis of eLORETA detected significantly higher NPV values at the high convexity area in the beta frequency band between 17 shunt responders and 19 non-responders. Considering our present and past research findings about NPV, we also discuss the advantage of this application of NPV representing a sensitive early warning signal of cortical impairment. Overall, our findings demonstrated that EEG has another dimension — that of NPV, which contains a lot of information about cortical electrical activity that can be useful in clinical practice.

1.AbstractThis work provides a framework based on multivariate autoregressive modeling for linear causal filtering in the sense of Granger. In its bivariate form, the linear causal filter defined here takes as input signals A and B, and it filters out the causal effect of B on A, thus yielding two new signals only containing the Granger-causal effect of A on B. In its general multivariate form for more than two signals, the effect of all indirect causal connections between A and B, mediated by all other signals, are accounted for, partialled out, and filtered out also. The importance of this filter is that it enables the estimation of directional measures of causal information flow from any non-causal, non-directional measure of association. For instance, based on the classic coherence, a directional measure of strength of information flow from A to B is obtained when applied to the linear causal filtered pair containing only A to B connectivity information. This particular case is equivalent to the isolated effective coherence (doi.org/10.3389/fnhum.2014.00448). Of more recent interest are the large family of phase-phase, phase-amplitude, and amplitude-amplitude cross-frequency coupling measures which are non-directional. The linear causal filter makes it now possible to estimate the directional causal versions these measures of association. One important field of application is in brain connectivity analysis based on cortical signals of electric neuronal activity (e.g. estimated sources of EEG and MEG, and invasive intracranial ECoG recordings). The linear causal filter introduced here provides a novel solution to the problem of estimating the direction of information flow from any non-directional measure of association. This work provides definitions, non-ambiguous equations, and clear prescriptions for implementing the linear causal filter in diverse settings.

1.AbstractSignals of brain electric neuronal activity, either invasively measured or non-invasively estimated, are commonly used for connectivity inference. One popular methodology assumes that the neural dynamics follow a multivariate autoregression, where the autoregressive coefficients represent the couplings among regions. If observation noise is present and ignored, as is common in practice, the estimated couplings are biased, affecting all forms of Granger-causality inference, both in time and in frequency domains. Significant nonsense coupling, i.e., nonsense connectivity, can appear when in reality there is none, since there is always observation noise in two possible forms: measurement noise, and activity from other brain regions due to volume conduction and low spatial resolution. This problem is critical, and is currently not being addressed, calling into question the validity of many Granger-causality reports in the literature. An estimation method that accounts for noise is based on an overdetermined system of high-order multivariate Yule-Walker equations, which give reduced variance estimators for the coupling coefficients of the unobserved signals. Simulation-based comparisons to other published methods are presented, demonstrating its adequate performance. In addition, simulation results are presented for a zero connectivity case with noisy observations, where the new method correctly reports no connectivity while classical analyses (as found in most software packages) report nonsense connectivity. For the sake of reproducible research, the supplementary material includes, in human readable format, all the time series data used here.

Objective Huntington’s disease (HD) is characterized by psychiatric, cognitive, and motor disturbances. The study aimed to determine electroencephalography (EEG) global state and microstate changes in HD and their relationship with cognitive and behavioral impairments. Methods EEGs from 20 unmedicated HD patients and 20 controls were compared using global state properties (connectivity and dimensionality) and microstate properties (EEG microstate analysis). For four microstate classes (A, B, C, D), three parameters were computed: duration, occurrence, coverage. Global- and microstate properties were compared between groups and correlated with cognitive test scores for patients. Results Global state analysis showed reduced connectivity in HD and an increasing dimensionality with increasing HD severity. Microstate analysis revealed parameter increases for classes A and B (coverage), decreases for C (occurrence) and D (coverage and occurrence). Disease severity and poorer test performances correlated with parameter increases for class A (coverage and occurrence), decreases for C (coverage and duration) and a dimensionality increase. Conclusions Global state changes may reflect higher functional dissociation between brain areas and the complex microstate changes possibly the widespread neuronal death and corresponding functional deficits in brain regions associated with HD symptomatology. Significance Combining global- and microstate analyses can be useful for a better understanding of progressive brain deterioration in HD.

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric disease characterized by gait disturbance, cognitive deterioration and urinary incontinence associated with excessive accumulation of cerebrospinal fluid (CSF) in the brain ventricles. These symptoms, in particular gait disturbance, can be potentially improved by shunt operation in the early stage of the disease, and the intervention associates with a worse outcome when performed late during the course of the disease. Despite the variable outcome of shunt operation, noninvasive presurgical prediction methods of shunt response have not been established yet. In the present study, we used normalized power variance (NPV), a sensitive measure of the instability of cortical electrical activity, to analyze cortical electrical activity derived from EEG data using exact-low-resolution-electromagnetic-tomography (eLORETA) in 15 shunt responders and 19 non-responders. We found that shunt responders showed significantly higher NPV values at high-convexity areas in beta frequency band than non-responders. In addition, using this difference, we could discriminate shunt responders from non-responders with leave-one-subject-out cross-validation accuracy of 67.6% (23/34) [positive predictive value of 61.1% (11/18) and negative predictive value of 75.0% (12/16)]. Our findings indicate that eLORETA-NPV can be a useful tool for noninvasive prediction of clinical response to shunt operation in patients with iNPH.

Brahma Kumaris Rajayoga’s open eyed ‘seed stage meditation’ was studied in 52 meditators. Meditation stages: concentration on peace, realization of being a soul and communion with the Supreme Soul. Frequency domain brain electric source localization was used on multichannel EEG recordings to establish activation differences between meditation and open eyed, task-free resting. Additional exploratory analyses probed for effects of passing time from initial rest through meditation to final rest. Meditation showed reduced activity in delta and increased activity in low alpha frequencies. Affected brain areas comprised the following networks: central executive network, mirroring network, task-positive and task-negative network. These altered activations reflect the main cognitive-affective and behavioral specifics of seed stage meditation: attention modulation, self-related processing, experiencing the soul as a point of light between the eyes, endowing the soul with the properties (peacefulness) of the Supreme Soul. Future studies need to differentiate between the stages of the meditation.

Highlights • We aimed to detect EEG changes induced by meditative interventions in PTRD subjects. • PTRD subjects exhibited increased gamma activity in the IPL relative to controls. • Changes of delta activity in the precuneus correlated with changes of the QOL scale., Objective Neurophysiological changes related to meditation have recently attracted scientific attention. We aimed to detect changes in electroencephalography (EEG) parameters induced by a meditative intervention in subjects with post-traumatic residual disability (PTRD), which has been confirmed for effectiveness and safety in a previous study. This will allow us to estimate the objective effect of this intervention at the neurophysiological level. Methods Ten subjects with PTRD were recruited and underwent psychological assessment and EEG recordings before and after the meditative intervention. Furthermore, 10 additional subjects were recruited as normal controls. Source current density as an EEG parameter was estimated by exact Low Resolution Electromagnetic Tomography (eLORETA). Comparisons of source current density in PTRD subjects after the meditative intervention with normal controls were investigated. Additionally, we compared source current density in PTRD subjects between before and after meditative intervention. Correlations between psychological assessments and source current density were also explored. Results After meditative intervention, PTRD subjects exhibited increased gamma activity in the left inferior parietal lobule relative to normal controls. In addition, changes of delta activity in the right precuneus correlated with changes in the psychological score on role physical item, one of the quality of life scales reflecting the work or daily difficulty due to physical problems. Conclusions These results show that the meditative intervention used in this study produces neurophysiological changes, in particular the modulation of oscillatory activity of the brain. Significance Our meditative interventions might induce the neurophysiological changes associated with the improvement of psychological symptoms in the PTRD subjects.

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric disease characterized by gait disturbance, cognitive dysfunction, and urinary incontinence that affects a large population of elderly people. These symptoms, especially gait disturbance, can potentially be improved by cerebrospinal fluid (CSF) drainage, which is more effective if performed at an early stage of the disease. However, the neurophysiological mechanisms of these symptoms and their recovery by CSF drainage are poorly understood. In this study, using exact low-resolution brain electromagnetic tomography-independent component analysis (eLORETA-ICA) with electroencephalography (EEG) data, we assessed activities of five EEG resting-state networks (EEG-RSNs) in 58 iNPH patients before and after drainage of CSF by lumbar puncture (CSF tapping). In addition, we assessed correlations of changes in these five EEG-RSNs activities with CSF tapping–induced changes in iNPH symptoms. The results reveal that compared with 80 healthy controls, iNPH patients had significantly decreased activities in the occipital alpha rhythm, visual perception network, and self-referential network before CSF tapping. Furthermore, CSF tapping–induced changes in occipital alpha activity correlated with changes in postural sway and frontal lobe function. Changes in visual perception network activity correlated with changes in gait speed. In addition, changes in memory perception network activity correlated with changes in Parkinsonian gait features. These results indicate a recruitment of cognitive networks in gait control, and involvement of the occipital alpha activity in cognitive dysfunction in iNPH patients. Based on these findings, eLORETA-ICA with EEG data can be considered a noninvasive, useful tool for detection of EEG-RSN activities and for understanding the neurophysiological mechanisms underlying this disease.

The aim of this study was to investigate the changes of brain electric field induced by symptom provocation in patients with obsessive-compulsive disorder (OCD) in comparison to healthy controls in the resting state. For this purpose, EEG recordings in conditions of initial rest, clean control, symptom provocation by imaginal exposure, and final rest were used for computing spatiotemporal activity characteristics based on microstate segmentation. Within-group comparisons were significant for the symptom provocation condition: OCD showed high global field power (GFP) and transition rates into a medial frontal microstate, whereas healthy controls showed high frequency of occurrence and high percent of dwelling time for a medial occipitoparietal microstate. Between-group comparisons demonstrated significantly lower GFP and dwelling time for the medial occipitoparietal microstate in OCD in several conditions including initial rest and symptom provocation. In addition, OCD compared to healthy controls showed significant instability of the medial occipitoparietal microstate, with high preference for transitions into the medial frontal microstate. In conclusion, during rest and symptom provocation, OCD patients make preferential use of a medial frontal brain network, with concomitant reduction of use of a medial occipitoparietal network, as shown by dwelling times, explained variance, and dynamic transition rates. These findings support the idea of a possible biological marker for OCD, which might correspond to pathological hyperactivation of the frontal control network.

Transcranial direct current stimulation is a promising neuromodulation method for treating depression. However, compared with pharmacological treatment, previous studies have reported that a relatively limited proportion of patients respond to tDCS treatment. In addition, the neurophysiological mechanisms underlying tDCS treatment remain unclear, making it difficult to identify response predictors for tDCS treatment based on neurophysiological function. Because treatment effects are achieved by repetitive application of tDCS, studying the immediate effects of tDCS in depressive patients could extend understanding of its treatment mechanisms. However, immediate changes in a single session of tDCS are not well documented. Thus, in the current study, we focused on the immediate impact of tDCS and its association with pre-stimulus brain activity. To address this question, we applied anodal tDCS to the left dorsolateral prefrontal cortex (DLPFC) or dorsomedial prefrontal cortex (DMPFC) in 14 patients with major depressive disorder (MDD) and 19 healthy controls (HCs), at an intensity of 1.0 mA for 20 min in a single session. To evaluate anxiety, the state trait anxiety inventory was completed before and after tDCS. We recorded resting electroencephalography before tDCS, and calculated electrical neuronal activity in the theta and alpha frequency bands using standardized low-resolution electromagnetic tomography. We found that, during application of left DLPFC tDCS to patients with MDD, the anxiety reduction effect of tDCS was related to higher baseline theta-band activity in the rostral anterior cingulate cortex (rACC) and no medication with benzodiazepine used as hypnotic. For DMPFC stimulation in MDD, the anxiety reduction effect was associated with lower baseline alpha-band activity in the left inferior parietal lobule. In contrast, in HCs, the anxiety reduction effect was associated with higher baseline alpha activity in the precuneus during DMPFC stimulation. The current results suggest that the association between pre-tDCS brain activity and the anxiety reduction effect of tDCS depends on psychopathology (depressed or non-depressed) as well as the site of stimulation (DMPFC or left DLPFC) and insomnia. Furthermore, the results suggest that tDCS response might be associated with baseline resting state electrophysiological neural activity.

Recently, cerebrospinal fluid (CSF) biomarkers related to Alzheimer’s disease (AD) have garnered a lot of clinical attention. To explore neurophysiological traits of AD and parameters for its clinical diagnosis, we examined the association between CSF biomarkers and electroencephalography (EEG) parameters in 14 probable AD patients. Using exact low-resolution electromagnetic tomography (eLORETA), artifact-free 40-sesond EEG data were estimated with current source density (CSD) and lagged phase synchronization (LPS) as the EEG parameters. Correlations between CSF biomarkers and the EEG parameters were assessed. Patients with AD showed significant negative correlation between CSF beta-amyloid (Aβ)-42 concentration and the logarithms of CSD over the right temporal area in the theta band. Total tau concentration was negatively correlated with the LPS between the left frontal eye field and the right auditory area in the alpha-2 band in patients with AD. Our study results suggest that AD biomarkers, in particular CSF Aβ42 and total tau concentrations are associated with the EEG parameters CSD and LPS, respectively. Our results could yield more insights into the complicated pathology of AD.

Background: Photophobia is a common feature of migraine, which may involve abnormal cortical information processing. In electroencephalograms (EEG), photic driving is known as a reaction to visual stimulation. Both photophobia and photic driving response are present during light stimulation. We hypothesized that cortical response to photic stimulation would differ between migraine patients with and without aura. Methods: We recruited 50 migraine patients (migraine with aura [MWA] = 21; migraine without aura [MWOA] = 29). Spontaneous eyes-closed resting EEG from 20 electrodes on the scalp during the interictal phase was recorded. After recording, each photic stimulation was separately selected. We analyzed EEG by fast Fourier transform and observed the spectrum frequency peaks and topographies in response to photic stimulation. Exact low-resolution electromagnetic tomography (eLORETA) was used to compute the 3-dimensional intracerebral distribution of EEG activity. Results: Photic stimulation at frequencies 5, 8, 15, and 20 Hz showed significant differences between migraine patients with and without aura. MWOA patients consistently had a stronger response to photic stimulation than MWA patients. In all patients, the differential response was located in the visual cortex, except for the stimulation at 20 Hz, where the difference at subharmonic 10 Hz was located in the parietal cortex (Brodmann Area 7). Conclusion: We confirmed high incidences of photic hypersensitivity and photic driving responses in migraine patients. We suggest that repeated occurrences of cortical spreading depression in MWA may suppress cortical function, thus contributing to a weaker visual cortical response to photic stimulation in MWA patients compared with MWOA patients.

Item does not contain fulltext Studies have shown that specific networks (default mode network [DMN] and task positive network [TPN]) activate in an anticorrelated manner when sustaining attention. Related EEG studies are scarce and often lack behavioral validation. We performed independent component analysis (ICA) across different frequencies (source-level), using eLORETA-ICA, to extract brain-network activity during resting-state and sustained attention. We applied ICA to the voxel domain, similar to functional magnetic resonance imaging methods of analyses. The obtained components were contrasted and correlated to attentional performance (omission errors) in a large sample of healthy subjects (N = 1397). We identified one component that robustly correlated with inattention and reflected an anticorrelation of delta activity in the anterior cingulate and precuneus, and delta and theta activity in the medial prefrontal cortex and with alpha and gamma activity in medial frontal regions. We then compared this component between optimal and suboptimal attentional performers. For the latter group, we observed a greater change in component loading between resting-state and sustained attention than for the optimal performers. Following the National Institute of Mental Health Research Domain Criteria (RDoC) approach, we prospectively replicated and validated these findings in subjects with attention deficit/hyperactivity disorder. Our results provide further support for the "default mode interference hypothesis". 9 p.

1.AbstractWhat is the role of each node in a system of many interconnected nodes? This can be quantified by comparing the dynamics of the nodes in the intact system, with their modified dynamics in the edited system, where one node is deleted. In detail, the spectra are calculated from a causal multivariate autoregressive model for the intact system. Next, without re-estimation, one node is deleted from the model and the modified spectra at all other nodes are re-calculated. The change in spectra from the edited system to the intact system quantifies the role of the deleted node, giving a measure of its Granger-causal effects (CFX) on the system. A generalization of this novel measure is available for networks (i.e. for groups of nodes), which quantifies the role of each network in a system of many networks. For the sake of reproducible research, program codes (PASCAL), executable file, and toy data in human readable format are included in the supplementary material.

1AbstractThe problem of interest here concerns electrophysiological signals from two cortical sites, acquired as invasive intracranial recordings, or from non-invasive estimates of cortical electric neuronal activity computed from EEG or MEG recordings (see e.g. https://doi.org/10.1101/269753). In the absence of other sources, these measured signals consist of an instantaneous linear mixture of the true, actual, unobserved local signals, due to low spatial resolution and volume conduction. A connectivity measure is unreliable as a true indicator of electrophysiological connectivity if it is not invariant to mixing, or if it reports a significant connection for a mixture of independent signals. In (Vinck et al 2011 Neuroimage 55:1548) it was shown that coherence, imaginary coherence, and phase locking value are not invariant to mixing, while the phase lag index (PLI) and the weighted version (wPLI) are invariant to mixing. Here we show that the lagged coherence (LagCoh) measure (2007, https://arxiv.org/abs/0711.1455), not studied in Vinck et al, is invariant to mixing. Additionally, we present here a new mixture-invariant connectivity statistic: the “standardized imaginary covariance” (sImCov). We also include in the comparisons the directed PLI (dPLI) by Stam et al (2012 Neuroimage 62:1415). Fourier coefficients for “N” trials are generated from a linear unidirectional causal time domain model with electrophysiological delay “k” and regression coefficient “b”. 1000 random data sets of “N” trials are simulated, and for each one, and for each connectivity measure, non-parametric randomization tests are performed. The “true positive detection rate” is calculated as the fraction of 1000 cases that have significant connectivity at p

Objectives: eLORETA (exact low-resolution brain electromagnetic tomography) is a technique created by Pascual-Marqui et al. [Int J Psychophysiol. 1994 Oct; 18(1): 49–65] for the 3-dimensional representation of current source density in the brain by electroencephalography (EEG) data. Kurtosis analysis allows for the identification of spiky activity in the brain. In this study, we focused on the evaluation of the reliability of eLORETA kurtosis analysis. For this purpose, the results of eLORETA kurtosis source localization of paroxysmal activity in EEG were compared with those of eLORETA current source density (CSD) analysis of EEG data in 3 epilepsy patients with partial seizures. Methods: EEG was measured using a digital EEG system with 19 channels. We set the bandpass filter at traditional frequency band settings (1–4, 4–8, 8–15, 15–30, and 30–60 Hz) and 5–10 and 20–70 Hz and performed eLORETA kurtosis to compare the source localization of paroxysmal activity with that of visual interpretation of EEG data and CSD analysis of eLORETA in focal epilepsy patients. Results: The eLORETA kurtosis analysis of EEG data preprocessed by bandpass filtering from 20 to 70 Hz and traditional frequency band settings did not show any discrete paroxysmal source activity compatible with the results of CSD analysis of eLORETA. In all 3 cases, eLORETA kurtosis analysis filtered at 5–10 Hz showed paroxysmal activities in the theta band, which were all consistent with the visual inspection results and the CSD analysis results. Discussion: Our findings suggested that eLORETA kurtosis analysis of EEG data might be useful for the identification of spiky paroxysmal activity sources in epilepsy patients. Since EEG is widely used in the clinical practice of epilepsy, eLORETA kurtosis analysis is a promising method that can be applied to epileptic activity mapping.

OBJECTIVE The objective of the study is to investigate the electrocortical and the global cognitive effects of 3 months rivastigmine medication in a group of mild to moderate Alzheimer's disease patients. MATERIALS AND METHODS Multichannel EEG and cognitive performances measured with the Mini Mental State Examination in a group of 16 patients with mild to moderate Alzheimer's Disease were collected before and 3 months after the onset of rivastigmine medication. RESULTS Spectral analysis of the EEG data showed a significant power decrease in the delta and theta frequency bands during rivastigmine medication, i.e., a shift of the power spectrum towards 'normalization'. Three-dimensional low resolution electromagnetic tomography (LORETA) functional imaging localized rivastigmine effects in a network that includes left fronto-parietal regions, posterior cingulate cortex, bilateral parahippocampal regions, and the hippocampus. Moreover, a correlation analysis between differences in the cognitive performances during the two recordings and LORETA-computed intracortical activity showed, in the alpha1 frequency band, better cognitive performance with increased cortical activity in the left insula. CONCLUSION The results point to a 'normalization' of the EEG power spectrum due to medication, and the intracortical localization of these effects showed an increase of cortical activity in frontal, parietal, and temporal regions that are well-known to be affected in Alzheimer's disease. The topographic convergence of the present results with the memory network proposed by Vincent et al. (J. Neurophysiol. 96:3517-3531, 2006) leads to the speculation that in our group of patients, rivastigmine specifically activates brain regions that are involved in memory functions, notably a key symptom in this degenerative disease.

1.AbstractEEG/MEG neuroimaging consists of estimating the cortical distribution of time varying signals of electric neuronal activity, for the study of functional localization and connectivity. Currently, many different imaging methods are being used, with very different capabilities of correct localization of activity and of correct localization of connectivity. The aim here is to provide a guideline for choosing the best (i.e. least bad) imaging method. This first study is limited to the comparison of the following methods for EEG signals: sLORETA and eLORETA (standardized and exact low resolution electromagnetic tomography), MNE (minimum norm estimate), dSPM (dynamic statistical parametric mapping), and LCMVBs (linearly constrained minimum variance beamformers). These methods are linear, except for the LCMVBs that make use of the quadratic EEG covariances. To achieve a fair comparison, it is assumed here that the generators are independent and widely distributed (i.e. not few in number), giving a well-defined theoretical population EEG covariance matrix for use with the LCMVBs. Measures of localization error, false positive activity, and false positive connectivity are defined and computed under ideal no-noise conditions. It is empirically shown with extensive simulations that: (1) MNE, dSPM, and all LCMVBs are in general incapable of correct localization, while sLORETA and eLORETA have exact (zero-error) localization; (2) the brain volume with false positive activity is significantly larger for MN, dSPM, and all LCMVBs, as compared to sLORETA and eLORETA; and (3) the number of false positive connections is significantly larger for MN, dSPM, all LCMVBs, and sLORETA, as compared to eLORETA. Non-vague and fully detailed equations are given. PASCAL program codes and data files are available. It is noted that the results reported here do not apply to the LCMVBs based on EEG covariance matrices generated from extremely few generators, such as only one or two independent point sources.